Low levels of antipertussis antibodies plus lack of history of pertussis correlate with susceptibility after household exposure to Bordetella pertussis
Introduction
Placebo-controlled efficacy trials in Sweden 1992–1995 [1] and Italy 1992–1995 [2] have shown multicomponent acellular pertussis vaccines (Pa) to be efficacious. Even without booster vaccinations, the vaccine-induced protection lasts up to 5 years after three doses of Pa [3], [4].
Immunity against pertussis is multifactorial, involving different arms of the immune response. Therefore, the scientific community does not recognize a single, common surrogate marker of protection against pertussis [5].
During the 1992–1995 trials in Sweden and Germany sera were systematically collected from vaccinated study children both before and after exposure to Bordetella pertussis [1], [6]. Results have been published elsewhere, indicating that antibodies against pertactin, fimbriae 2 and 3 and to a lesser extent pertussis toxin (PT) were correlated with short-term protection in small children [7], [8]. Other surveillance studies [9], [10] and animal experiments [11], [12] show also filamentous hemagglutinin (FHA) to be correlated with protection.
Sweden had discontinued universal mass vaccination against pertussis in 1979, and we knew that most adolescents and adults had been exposed to natural pertussis repeatedly during the previous decade [13]. Swedish clinical experience [13], [14] as well as previous household studies had demonstrated subclinical and asymptomatic pertussis to be a common phenomenon [15], [16].
One of the general aims in the Swedish 1992–1995 trial was to study parameters linked with susceptibility—not only in small children but also in other household members. However, because of the great size of the trial true pre-exposure sera could not be collected systematically in all the older household members. Instead extensive early sampling was done in the households whenever pertussis was diagnosed, irrespective of symptoms [1]. It was thought that active surveillance would provide good opportunities to obtain an early initial blood sample and thereby a good chance to demonstrate early rises of antipertussis antibody titers. It was, therefore, deemed worthwhile to try to investigate possible serological correlates of susceptibility even for older children, adolescents and adults.
Section snippets
Vaccines
In the Swedish 1992–1995 efficacy trial, 9829 study infants received three doses of combination vaccines against diphtheria (D), tetanus (T), and three out of four children were randomized to receive vaccine also against pertussis (P) [1]. Two different DTPa vaccines were used: a two-component PT/FHA vaccine produced by GlaxoSmithKline Biologicals and a five-component PT/FHA/Pertactin/Fim 2 and 3 vaccine produced by Aventis Pasteur Ltd. A third group was vaccinated with a DTP whole cell vaccine
Transmission of pertussis
This paper gives data on 808 exposed individuals (Table 2). The majority (608/808) was born before 1979 and had previously received a Swedish-produced DTPw vaccine during childhood. Most (approximately 85%) of the 200 individuals born after 1978 had never been vaccinated against pertussis.
Laboratory confirmed pertussis occurred in 272/808 persons (34%) (Table 3, Table 4). After exclusion of individuals without paired serology, the rate of laboratory confirmed pertussis was estimated as 41%
Transmission of pertussis
With the laboratory criteria given in Table 1, 41% of the exposed household members with paired sera were diagnosed as “laboratory confirmed pertussis”. Many of those persons had mild symptoms, and they probably would not have been diagnosed as pertussis outside of a clinical trial. There is also the possibility that the laboratory criteria chosen were not sensitive enough, because previous household studies with similar design have reported higher rates than in our study. In an American study,
Concluding remarks
Asymptomatic or subclinical pertussis is a common phenomenon after household exposure to B. pertussis. Susceptibility to symptomatic pertussis among older household members was statistically significantly correlated with low or non-measurable levels of IgG anti-PT in initial blood samples. Also anti-pertactin antibodies and anamnestic data on previous pertussis vaccination or disease could be used as meaningful predictive variables in a multifactorial analysis.
A pragmatic approach for improving
Acknowledgements
This study was done under a contract (N01-AI-15125) with the US National Institute of Allergy and Infectious Diseases. We thank Norman Begg for critical reading of the manuscript. Conflict of interest: after the termination of the household study, Jann Storsaeter was employed by GlaxoSmithKline, Sweden.
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