Changes in genetic diversity of the Bordetella pertussis population in the United Kingdom between 1920 and 2006 reflect vaccination coverage and emergence of a single dominant clonal type

Abstract

Pertussis (whooping cough) is a potentially fatal respiratory disease caused by the bacterium Bordetella pertussis. Despite effective vaccination programs, there has been concern in some developed countries that pertussis cases are on the increase. We characterized 703 clinical B. pertussis isolates collected in the United Kingdom between 1920 and 2006 using multilocus variable-number tandem repeat analysis (MLVA), pertactin (prnA) and pertussis toxin (ptxA) genotyping, and serotyping. The results showed that the genetic diversity of the bacterial population decreased during periods of high vaccine coverage. However, it was elevated between 1977 and 1986, when vaccine coverage in the United Kingdom was low and epidemics occurred. A high proportion of MLVA types during this epidemic period were novel, and the prnA(2) and prnA(3) alleles were seen for the first time in the United Kingdom. MLVA-27 appeared in 1982, was codominant during the 1998-to-2001 period, and comprised approximately 70% of isolates during both the 2002-to-2004 and the 2005-to-2006 periods. The United Kingdom is dominated currently by an MLVA-27 prnA(2) ptxA(1) serotype Fim3 clonal type. Even during recent periods dominated by MLVA-27, many novel types were found at low frequencies, suggesting that either there are a large number of uncommon MLVA types circulating at low frequencies or new types are constantly arising. This supports a hypothesis that MLVA-27 is under some form of positive selection conferring increased survival in a highly vaccinated population. There has been no significant change to the bacterial population in the first 2 years since the United Kingdom switched from a whole-cell to an acellular vaccine.

FIG. 1.

Minimum spanning trees showing the genetic diversity of the B. pertussis population from 1920 to 1956 (a), 1963 to 1967 (b), 1977 to 1986 (c), 1998 to 2001 (d), 2002 to 2004 (e), and 2005 to 2006 (f). Trees were derived from the six MLVA alleles. Each circle represents a unique MLVA type (shown by the number in the circle). The size of each circle illustrates the proportion of strains with that MLVA type (the smallest circle in each tree represents one isolate). Thick lines separate SLVs, thin lines separate DLVs, and dotted lines signify a more distant relationship. Colors illustrate the combination of prnA and ptxA (see key). When more than one combination is present for a given MLVA type, the circle is divided proportionally in the form of a pie chart. The distribution of serotypes is given in an inset panel for each time period. It is also shown graphically in panels d to f (serotypes are separated by dotted lines).