Antigenic shift and increased incidence of meningococcal disease.
BACKGROUND
The 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.


METHODS
We 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.


RESULTS
For 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.


CONCLUSIONS
Antigenic 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.
Harrison
Lee H
LH
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. lharriso@edc.pitt.edu
Jolley
Keith A
KA
Shutt
Kathleen A
KA
Marsh
Jane W
JW
O'Leary
Mary
M
Sanza
Laurie Thomson
LT
Maiden
Martin C J
MC
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000940:Antigenic Variation / Q000235:genetics*; D000942:Antigens, Bacterial / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D005798:Genes, Bacterial; D006801:Humans; D015994:Incidence; D008589:Meningococcal Infections / Q000453:epidemiology* / Q000276:immunology / Q000382:microbiology*; D008969:Molecular Sequence Data; D009154:Mutation; D009345:Neisseria meningitidis / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D018272:Porins / Q000235:genetics
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; C093120:FrpB protein, bacteria; D018272:Porins; C057699:porin protein, Neisseria