PEDIATRICS Vol. 108 No. 5
November 2001,
p. e81
ELECTRONIC ARTICLE:
Sustained Efficacy During the First 6 Years of Life of
3-Component Acellular Pertussis Vaccines Administered in Infancy:
The Italian Experience
Received Mar 28, 2001; accepted Jun 18, 2001.
Stefania Salmaso*,
Paola Mastrantonio
,
Alberto E. Tozzi*,
Paola Stefanelli,
Alessandra Anemona*,
Marta L. Ciofi degli Atti*,
Anna Giammanco§, and
the Stage III Working Group
From the Laboratories of * Epidemiology and Biostatistics and
Bacteriology and Medical Mycology, Istituto Superiore di
Sanità, Rome, Italy; and § Department of Hygiene and
Microbiology, University of Palermo, Palermo, Italy.
Background. In 1992-1993, a
randomized, double-blind, placebo-controlled clinical trial of
two 3-component acellular pertussis vaccines was started in 4 of
Italy's 20 regions. During the trial, the children had been randomized
to receive 3 doses of 1 of 2 acellular pertussis vaccines combined with
diphtheria and tetanus toxoids (DT) or of a DT vaccine only, at 2, 4, and 6 months of age. Both diphtheria-tetanus-acellular pertussis
(DTaP) vaccines, 1 manufactured by SmithKline
Beecham (DTaP SB; Infanrix) and 1 manufactured by Chiron Biocine (DTaP CB; Triacelluvax),
contain pertussis toxin (PT), filamentous hemagglutinin, and pertactin.
The results of the first period of follow-up, which ended in 1994 (stage 1), showed that both vaccines had a protective efficacy of 84%
in the first 2 years of life; when the trial's follow-up was extended under partial blinding until the participating children had reached 33 months of age (stage 2 of the follow-up), these high levels of efficacy
had persisted. Therefore, the objective of this study was to estimate
the persistence of protection from 3 to 6 years of age of the 2 3-component DTaP vaccines administered as primary immunization in
infancy.
Methods. An unblinded prospective longitudinal study of
vaccinated and unvaccinated children in 4 Italian regions, with active
surveillance of cough, was conducted by study nurses, and Bordetella
pertussis infections were confirmed laboratory. The present study
(stage 3) included those children who completed stage 2 of the
follow-up and were still under active surveillance as of October 1, 1995, accounting for 4217 children who had received DTaP SB
(representing 94% of the vaccine's recipients in the initial phase of
the trial), 4215 who had received DTaP CB (95% of the original
recipients), and 266 who had received DT only (18% of the original
recipients). Because the parents of most of the original DT placebo
group accepted pertussis vaccination during stage 2 in 1995, an
additional 856 children were recruited in the DT group at the
initiation of stage 3. These additional children were identified from
the census list of children born in the same period and living in the
same areas as the trial participants but who had been vaccinated in
infancy with DT only. Eligible children were included in stage 3 if
they had no history of either pertussis or pertussis vaccination and if
a serum sample obtained at the time of enrollment had undetectable immunoglobulin G (IgG) against PT. Parental consent to participate in
the study was obtained. Active surveillance for pertussis was conducted
in the field by 72 study nurses through monthly contact with each
family in the study. A cough episode that lasted 
7 days was
considered to be a laboratory-confirmed infection by Bordetella
pertussis if at least 1 of the following 5 criteria (listed in
hierarchic order) was met: 1) B pertussis was obtained from nasopharyngeal culture (culture-confirmed infection); 2) the
enzyme-linked immunosorbent assay (ELISA) IgG or IgA titer against PT
in the convalescent-phase serum sample increased by at least 100%
compared with the acute-phase sample; 3) the PT-neutralizing titers in
Chinese hamster ovary assay in the convalescent-phase sample increased
by at least 4-fold compared with the acute-phase sample; 4) the ELISA
IgG or IgA titer against filamentous hemagglutinin in the
convalescent-phase sample increased by at least 100% and the culture
or the polymerase chain reaction assay on the nasopharyngeal aspirate
was negative for B parapertussis; and 5) the ELISA IgG PT titer in 1 of the 2 serum samples exceeded the geometric mean titer
computed on convalescent sera of the children with a culture-confirmed B pertussis infection in each study group. Incidence of
laboratory-confirmed B pertussis infection, using case
definitions that varied in terms of duration and type of cough, was
computed and the proportion of cases prevented among DTaP recipients in
comparison with DT recipients was calculated.
Results. A total of 391 laboratory-confirmed infections
were identified in the 3-year follow-up period (138 DTaP SB, 126 DTaP
CB, 127 DT recipients, respectively). The mean duration of cough in
children with laboratory-confirmed infection was 48, 47, and 70 days
for the DTaP SB, DTaP CB, and DT recipients, respectively; the mean duration of spasmodic cough was 15, 13, and 23 days, respectively. When
using the primary case definition (ie, laboratory-confirmed B
pertussis infection and 14 days of spasmodic cough or 21
days of any cough), the efficacy was 78% for the DTaP SB vaccine (95% confidence interval [CI]: 71%-83%) and 81% for the DTaP CB
vaccine (95% CI: 74%-85%). When using the case definition based on
a more severe clinical presentation (21 days of spasmodic cough), the vaccine efficacy was 86% (95% CI: 79%-91%) for both vaccines. When
using the case definition based on milder clinical presentation (any
cough for 7 days), the efficacy was 76% (95% CI: 69%-81%) for
the DTaP SB vaccine and 78% (95% CI: 72%-83%) for the DTaP CB
vaccine.
Conclusions. The persistence of protection through 6 years
of age suggests that the fourth DTaP dose could be postponed until
preschool age in children who received 3-component acellular pertussis
vaccines in infancy, provided that immunity to diphtheria and tetanus
is maintained. Additional booster doses could be administered at older
ages to reduce reactogenicity induced by multiple administrations and
to optimize the control of pertussis in adolescents and young adults.
Key words:
pertussis,
acellular vaccine,
efficacy,
follow-up,
prospective study,
children.
