October 2000
BILTHOVEN, Netherlands - Attempting to explain a 1996 outbreak of pertussis in the highly vaccinated population of this country, researchers here analyzed surveillance data and concluded that antigenic changes in Bordetella pertussis combined with the small immunogenicity profile of the Dutch vaccine may be to blame.
"Pertussis remains endemic in the Netherlands and epidemic peaks occur despite high vaccination coverage," said lead researcher of the study Hester de Melker, epidemiologist in the department of infectious disease epidemiology at the National Institute of Public Health and the Environment here. "After the unexpected high epidemic peak in 1996, the incidence in the Netherlands has remained higher than it was before 1996. This recent increase is not fully understood. However, the surveillance data support that the recently detected antigenic changes in the B. pertussis population may play a role."
The researchers observed a decrease in estimated vaccine effectiveness, beginning in 1993 and bottoming out in 1996. This manifested as a shift in pertussis incidence toward older, vaccinated age groups in 1996 and 1997. The age-specific peak incidence shifted to 4-year-old children in those years, whereas from 1989 to 1995, the average annual incidence as determined by case reporting and serologic testing was highest for infants younger than 1 year.
This could only partly be explained by the enhanced application of positive one-point serology as a method of diagnosis, which began in 1997. Plus, according to the researchers, the increase in reported cases among vaccinated patients actually started two years before the 1996 outbreak, suggesting a mismatch between circulating strains and vaccine strains.
The researchers argued that increasing or decreasing reports of pertussis cases and data on positive serology are likely to reflect true changes in incidence when they are accompanied by similar trends in hospitalizations. In 1996, the increase in pertussis incidence among children younger than 1 (who were mostly unvaccinated) was similar to the increase in hospital admissions.
"Hospitalizations concern the youngest, but they are a reflection of `rate of transmission' or `intensity of circulation' of B. pertussis in the population - of all ages," said de Melker.
Among older, mostly vaccinated patients, the increase in hospital admissions was relatively small, but the increase in pertussis incidence was higher among vaccinated than among unvaccinated people of all ages.
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The team compared case-reporting data from the Inspectorate of Health from January 1976 to September 1998 with three other types of surveillance data: deaths, hospitalizations and positive serodiagnoses. Case-reporting data was influenced by changes over the years: A case definition was introduced in 1988, and in 1997, positive polymerase chain reaction (PCR) and positive one-point serology were both allowed as laboratory confirmation (in addition to positive culture and positive two-point serology).
Data on pertussis serology was obtained from the National Institute of Public Health and the Environment on patients whose date of disease onset fell between January 1989 and September 1998 and those whose date of serologic result was between January 1986 and December 1987. Patients with positive two-point serology in 1989 to 1998 and patients with positive one-point serology in 1994 to 1998 were selected. The criteria for positive one-point serology were retrospectively applied to the serologic data of 1986-87 and 1989-93. The distribution of cases in 1986 and 1987 was calculated based on the year of the test result and, in 1989-1998, based on the year of first symptoms.
Vaccine effectiveness was measured among children ages 1 to 4 and 5 to 9 using the case reporting data from 1976 to 1997 and assuming an average vaccine coverage of 96%. Completely vaccinated children (those with at least three vaccinations) were compared with incompletely vaccinated or unvaccinated children.
For 1993 to 1997, the case-reports database and the serodiagnosis database were linked at the individual level to verify the type of serodiagnosis made (either one-point or two-point).
No sign of an abrupt deterioration of vaccine quality was found. However, changes of the bacterium, or antigenic divergence, for two important protective antigens, pertactin and pertussis toxin, were demonstrated by Frits Mooi, PhD, and his group at the National Institute of Public Health and the Environment. The Dutch whole-cell vaccine induces low levels of antibodies against pertussis toxin and filamentous hemagglutinin and high levels of antibodies to agglutinogens and pertactin. This profile may have left the Dutch population vulnerable to antigenic changes in B. pertussis, particularly with respect to pertactin, according to researchers.
The vaccine's production process was improved in November 1997. It was not possible to study the potential effects of this change on the surveillance data.
For more information:
- de Melker HE, Schellekens JFP, Neppelenbroek SE, et al. Reemergence of pertussis in the highly vaccinated population of the Netherlands: observations on surveillance data. Emerg Infect Dis. 2000;6(4):348-357.
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