A population genetic framework for the study of invasive diseases caused by serotype b strains of Haemophilus influenzae

One hundred seventy-seven isolates of serotype b Haemophilus influenzae recovered largely from children with invasive disease in the United States were characterized by the electrophoretic mobilities of 16 metabolic enzymes, the NaDodSO₄/PAGE pattern of outer-membrane proteins (OMP), and biotype. Thirty-two distinctive multilocus genotypes (electrophoretic types, ETs) were distinguished on the basis of allele profiles at the enzyme loci. Twenty-eight OMP types and five biotypes were identified, but only 55 distinctive combinations of ET, OMP type, and biotype were represented. The strong nonrandom associations of characters and the recovery of isolates with identical properties in widely separated geographic regions and over a 40-year period suggest that the population structure of H. influenzae is basically clonal. Examination of nonserotype b isolates indicated that clones of serotype b are a restricted subset of the genotypes in the species as a whole. Currently, most of the invasive H. influenzae disease in the United States is caused by serotype b strains of two related ETs and, more specifically, much of it is attributable to two subclones marked by OMP type. There is evidence that the frequeny of the ET-1/OMP 1H/biotype I subclone has increased dramatically in the United States since the 1939-1954 period. The hypothesis that populations of H. influenzae are subject to marked temporal variation in clonal composition is supported by evidence of major differences in the genetic structure of populations in the United States and the Netherlands.