Reemergence of Pertussis in the Highly Vaccinated Population of The Netherlands: Observations on Surveillance Data

Hester E. de Melker, J.F.P. Schellekens, S.E. Neppelenbroek, F.R. Mooi, H.C. Rümke, M.A.E. Conyn-van Spaendonck, National Institute of Public Health and the Environment, Bilthoven, the Netherlands

Disclosures

Emerging Infectious Diseases. 2000;6(4) 

In This Article

Discussion

The 1996 surveillance data show that the unexpected pertussis outbreak was detected not only by increased reporting of cases[5] but also by increased hospitalizations, cases with positive serology, and deaths. Vaccine effectiveness, which had already declined in 1994 and 1995, declined further in 1996 and 1997. According to case reports and serologic data, in 1996 the increase in pertussis incidence among (mostly unvaccinated) children <1 year of age was similar to the increase in hospitalizations. However, in older, mostly vaccinated persons the increase in hospitalizations was relatively small. Contrary to reports at the time, a somewhat smaller epidemic likely occurred in 1986 and 1987[16,17].

The surveillance data for pertussis in the Netherlands were affected by changes in availability and interpretation of serologic tests, case definitions for reporting, and case-reporting rate. However, by relying on various surveillance sources, applying criteria for one-point serology used in recent years to serologic data of 1986 and 1987, and matching our database of reported cases with our serodiagnosis database, we gained a better understanding about whether observed changes in surveillance data represented true changes in the underlying incidence of pertussis.

The trend in hospitalizations likely reflects the incidence of severe pertussis; however, this trend is probably less sensitive to changes in availability and interpretation of serologic tests, case definitions, and case-reporting rate. Thus, increasing or decreasing reports of pertussis case and data on positive serology are likely to (at least partially) reflect true changes when they are accompanied by similar trends in hospitalizations.

We obtained more insight into the effect of changes in definitions of positive serology and case definitions for reporting on serologic and reported data. The current, more restrictive, criteria for positivity of one-point serology were applied to serodiagnostic data of 1986 and 1987. It was possible to study changes in the rate of reported cases with positive one-point serology and cases with positive two-point serology in 1993 to 1997 by linking the case-reporting and serodiagnosis databases. Furthermore, stratifying case reports according to method of diagnosis led us to conclude that the decrease in estimated vaccine effectiveness and the shift in 1996 and 1997 toward older age-groups in the reported cases could only partly be explained by the enhanced application of positive one-point serology. Because of great variation in case definitions and types of laboratory confirmation, comparing numbers of reported cases in different countries is meaningless. Hospitalizations, although limited to severe pertussis cases, might be more useful for such international comparisons.

Our results clearly show that pertussis has remained endemic with epidemic peaks in the Netherlands, despite high vaccination coverage. Immunity after infection, as well as after vaccination, is not lifelong. Waning vaccine-induced immunity has been suggested as an explanation of the reemergence of the disease in other countries and probably has contributed to the pertussis epidemic in the 1980s and in 1996-97[18,19,20]. However, the outbreak in 1986-87 may also have been associated with the Dutch vaccine's temporary reduction in potency--from 16 to 10 opacity units per dose--in 1976 to 1984. The somewhat lower vaccine-effectiveness estimates in 1986 and 1987 might be explained by greater exposure to B. pertussis in epidemics than in interepidemic periods[21,22].

The remarkable increase of reported cases among vaccinated patients over a wide age range starting 2 years before the 1996 outbreak, suggests a mismatch between circulating strains and vaccine strains[5,7,8,9]. Antigenic divergence between vaccine strains and clinical isolates was observed for two important protective antigens, pertactin and pertussis toxin[9]. Furthermore, data suggest that the whole-cell vaccine protects better against strains with the pertactin vaccine type than against strains with nonvaccine types[9].

By analyzing serologic and hospitalization data apart from case-reporting data, we assessed the increase in pertussis incidence in 1996 among (mostly unvaccinated) children <1 year of age. The increase in incidence was accompanied by a similar increase in hospitalizations for pertussis in the same age-group, which indicates that the virulence of B. pertussis for unvaccinated and unexposed persons did not change during the outbreak.

In contrast, for older, mostly vaccinated persons, the increase in hospitalizations was smaller than the increase found in other surveillance sources. While the incidence of hospital admissions was highest for infants <1 year of age, the incidence in other surveillance sources was highest in 4-year-old children. Therefore, a greater proportion of infected vaccinated persons may have had clinical symptoms because of antigenic shifts, which probably led to greater transmission of bacteria and thus a greater degree of infection in the population. This is shown by the increase of cases in unvaccinated infants.

Despite the findings of antigenic variants of pertactin and pertussis toxin in other countries, no outbreaks similar to those in the Netherlands have been observed[23,24,25]. The vaccines in these countries may be potent enough to offset antigenic variation, or pertussis vaccines may protect less well against strains with pertactin profiles dominant in the Netherlands but less common elsewhere[23]. The Dutch vaccine has been used in the National Immunization Program since 1953. No sign of an abrupt deterioration of vaccine quality, as determined for product release by the mouse protection test, has been found[5]. However, 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[6]. This immunogenicity profile may have resulted in a greater vulnerability of the vaccinated Dutch population to antigenic changes in B. pertussis, especially with respect to pertactin. Since November 1997, the production process for the Dutch pertussis vaccine has been improved, resulting in a slightly higher expression of pertussis toxin. We have not yet studied the potential effect of this change.

Pertussis is also reemerging in Canada, where similar surveillance patterns may elucidate the role of the vaccine's immunogenicity profile[1,2,5]. These similarities are the small proportion of infants and large proportion of patients 1 to 9 years of age affected, estimates of low vaccine effectiveness, and lower levels of antibodies against pertussis toxin after vaccination with the Canadian whole-cell vaccine[20,26]. By contrast, the increase in pertussis cases in the United States is accompanied by greater proportions of affected infants and adults and more favorable vaccine-effectiveness estimates[22,27,28]. The levels of pertussis toxin antibodies after vaccination were higher for an American whole-cell vaccine than for Canadian whole-cell vaccines[26].

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