Temporal Trends in Bordetella pertussis Populations, Denmark, 1949–2010

Randi Føns Petersen

, Tine Dalby, Ditte Marie Dragsted, Frits Mooi, and Lotte Lambertsen

Author affiliations: Statens Serum Institut, Copenhagen, Denmark (R.F. Petersen, T. Dalby, L. Lambertsen); private practitioner, Frederiksberg, Denmark (D.M. Dragsted); National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands (F. Mooi)

Abstract

We used multilocus variable-number tandem repeat analysis and multiple antigen sequence typing to characterize isolates of Bordetella pertussis strains circulating in Denmark during periods with and without pertussis vaccination coverage. Our results show substantial shifts in the B. pertussis population over time and a reduction in genetic diversity. These changes might have resulted from the introduction of pertussis vaccines in Denmark and other parts of Europe. The predominant strains currently circulating in Denmark resemble those in other European countries.

Whooping cough is a vaccine-preventable disease caused by the bacterium Bordetella pertussis; however, the protection conferred by vaccination does not last throughout life. In Denmark, as in other industrialized countries with high vaccination coverage, the disease is still endemic despite ≈50 years of vaccination. In 1961, a whole-cell B. pertussis (wP) vaccine was introduced into the childhood vaccination schedule in Denmark. In January 1997, it was replaced by a monocomponent acellular B. pertussis (aP) vaccine (DiTeKiPol or DiTeKiPol/Act-Hib; Statens Serum Institut [SSI], Copenhagen, Denmark) containing hydrogen peroxide–inactivated B. pertussis toxoid as the sole pertussis antigen. This vaccine was originally described and patented by the National Institutes of Health (Bethesda, MD, USA) (1,2). In 2003, a booster dose for preschool-age children (5 years of age) was introduced (diTekiBooster or DiTeKiPol Booster; SSI). Coverage among infants in Denmark for the third dose of pertussis vaccine has traditionally been high (≈87%–91%) (3). Acellular pertussis vaccines can contain up to 5 different antigens from B. pertussis, and Denmark is the only country using a monocomponent vaccine for both primary and booster vaccination (4).
The incidences of whooping cough and related deaths in Denmark have decreased dramatically since the introduction of pertussis vaccines. During a whooping cough epidemic in the early 1950s, before vaccine was introduced, the incidence of infection was ≈11,000 per 100,000 infants (5). In 2010, however, the incidence of infection among infants 0–1 year old had dropped to 110 per 100,000 infants and the incidence among the whole population had dropped to 7 per 100,000 persons (6). In addition, the last 2 pertussis–related deaths among infants in Denmark were notified in 2010 and 2005 (7). In general, the population-wide incidence of whooping cough in Denmark has been low since implementation of the pertussis vaccination program. However, occasional epidemic peaks have occurred, and the latest 2 were in 2002 (incidence, 36 cases/100,000 persons) and 2004 (incidence, 24 cases/100,000 persons) (8).
To determine the predominant strains of B. pertussis circulating in Denmark, we characterized clinical isolates obtained during 3 periods. Period 1, comprised 1949–1961, the year vaccine was introduced; period 2 comprised 1962–1996, during which wP vaccine was used; and period 3 comprised the years after 1996, during which aP vaccine has been used. We characterized the isolates by using multilocus variable-number tandem repeat analysis (MLVA) and multiple antigen sequence typing (MAST) to partially sequence the genes encoding pertactin (prn), B. pertussis toxin S1 subunit (ptxA, also designated ptxS1), B. pertussis toxin promoter (ptxP), and tracheal colonization factor A (tcfA). Because there is no consensus about which genes should be included in MAST of B. pertussis, we designated the results obtained in Denmark as MASTdk.