BackgroundThe incidence of serogroup C and Y meningococcal disease increased in the United States during the 1990s. The cyclical nature of endemic meningococcal disease remains unexplained. The purpose of this study was to investigate the mechanisms associated with the increase in the incidence of meningococcal disease MethodsWe characterized an increasing incidence of invasive serogroup C and Y meningococcal disease using population-based surveillance from 1992 through 2001. Isolates were characterized by multilocus sequence typing and antigen sequence typing of 3 outer membrane protein (OMP) genes: porA variable regions (VRs) 1 and 2, porB, and fetA VR ResultsFor both serogroups, OMP antigenic shifts were associated with increased incidence of meningococcal disease. For serogroup Y, antigenic shift occurred through amino acid substitutions at all 3 OMPs—PorA VR 1 and 2, PorB, and FetA VR. For serogroup C, antigenic shift involved amino acid substitutions at FetA VR and, in some cases, deletion of the porA gene. On the basis of deduced amino acid sequences, the antigenic changes likely occurred by horizontal gene transfer ConclusionsAntigenic shifts were associated with increased incidence of serogroup C and serogroup Y meningococcal disease. For serogroup Y, the changes involved all OMP genes that were studied. Increases in the incidence of meningococcal disease may be caused, in part, by antigenic shift