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He Q, Viljanen MK, Arvilommi H, Aittanen B, Mertsola J. Whooping Cough Caused by Bordetella pertussis and Bordetella parapertussis in an Immunized Population. JAMA. 1998;280(7):635–637. doi:10.1001/jama.280.7.635
Context.— The prevalence of Bordetella pertussis and Bordetella parapertussis infections among outpatients in
an immunized population is not known.
Objective.— To study the prevalence of these infections in outpatients with paroxysmal
cough in Finland, where the pertussis vaccine coverage of 4 doses is 98%.
Design.— Prospective cohort study.
Setting.— Thirty-two health centers in southwestern Finland.
Patients.— A total of 584 patients with paroxysmal cough seen at local health centers
from October 1994 through March 1997 from whom nasopharyngeal swabs were collected.
Main Outcome Measures.— Prevalence of positive cultures for B pertussis
or B parapertussis and/or positive polymerase chain
reaction (PCR) results and frequency of symptoms in those with pertussis and
Results.— A total of 153 subjects (26.2%) had Bordetella
infection by culture or PCR: 93 (60.8%) had B pertussis infection, 49 (32.0%) had B parapertussis
infection, and 11 (7.2%) had both. Of these cases, 39 (25.5%) had positive
cultures and 95 (62.1%) had positive PCR results for B pertussis, and 19 (12.4%) had positive cultures and 55 (35.9%) had positive
PCR results for B parapertussis. At the time of diagnosis,
no difference was found in the frequency of symptoms between patients with B parapertussis infection and those with B pertussis infection. Bordetella parapertussis
infection was as common as B pertussis infection
in children before school entry, whereas in schoolchildren and adults, B pertussis infection was more common than B parapertussis infection (P<.001).
Conclusion.— Bordetella infections are common in an immunized
population, and B parapertussis infections apparently
are more prevalent than previously documented.
BORDETELLA pertussis and Bordetella parapertussis cause whooping cough in humans. They are almost
identical at the DNA level and produce many similar virulence factors. The
pathogenetically important difference between the two is that B parapertussis does not secrete pertussis toxin.1
In the prevaccination era, the relative frequency rates of B parapertussis isolates varied from 1% to 35% of Bordetella isolates,2-4
and similar frequency rates, from 2% to 25%, were also found during recent
acellular vaccine efficacy trials.5,6
Although cases of infection with B parapertussis,
even outbreaks, have been reported in immunized populations,4,7-11
community-based data on the occurrence of B parapertussis infection are limited. This study investigated the epidemiology of
both infections in a highly immunized population.
Bordetella pertussis vaccination was introduced
in Finland (population, 5.1 million) in 1952. Since 1958 the vaccine has contained
strain 18530. Because serotype 1.2 strains emerged in the 1970s, strain 1772
was introduced to the vaccine (v/v) in 1976. The vaccine is manufactured by
the National Public Health Institute, Helsinki, Finland, and contains 5 ×
109 formalin-killed B pertussis organisms per dose combined with diphtheria and tetanus toxoids. The
vaccine is used at 3, 4, 5, and 24 months, and the coverage is 98%.12
In the last 10 years, based on the report of the official reporting
system, the annual number of laboratory-confirmed B pertussis infection cases have ranged from 498 to 2574. Most patients are schoolchildren.
In the last decade, 648 patients with B pertussis
infection and 13 patients with B parapertussis infection
were hospitalized and 76% of them were younger than 1 year.
To collect more reliable data, we started an enhanced surveillance in
southwestern Finland (population, 702000) in October 1994 that lasted 30 months
and ended in March 1997. Swabs (calcium alginate), culture transport tubes,
and questionnaires were provided for all 32 health centers free of charge.
Culture results were reported to the health centers 7 days after the sample
arrived at our laboratory.
In Finland, the health centers are major sources for primary health
care of children and adults. There is at least 1 health center in each community.
The services offered by these centers are usually free.
In the health centers, nasopharyngeal specimens were taken by physicians
from all patients with paroxysmal cough, characterized as bouts of uncontrollable
coughing of any duration. During the 30 months of the study, swabs were obtained
from 584 eligible patients (number of male patients, 257; age range, 7 days
to 74 years; median age, 9 years). No hospitalization was needed.
At the time of sampling, 135 (23.1%) were experiencing whooping and 208 (35.6%)
were experiencing vomiting. Twenty-nine health centers (90.6%) sent samples
to the laboratory. The average number of samples obtained each month was 19
Detailed clinical information on each subject was obtained by a structured
questionnaire asking about the date of onset and the nature of symptoms. The
questionnaires were completed by physicians at the health centers and mailed
to the laboratory. The symptoms of subjects were not followed up after this
first contact with the health center.
The swabs were inoculated onto the slant of the transport medium (of
the same composition as the charcoal agar plate) supplemented with cephalexin,
placed in sterile empty tubes with caps, transported to the laboratory, and
stored at −40°C for polymerase chain reaction (PCR). Twenty swabs
were not sent to the laboratory after inoculation. Thus, 564 swabs were tested
Details of bacterial culture and identification, DNA extraction, and
PCR have been described earlier.11-14
Two sets of primers derived from insertion sequence elements IS481 and IS1001
that are specific for B pertussis and B parapertussis, respectively, were used for PCR assays.12,13
The 2 PCR assays were run separately. The parapertussis PCR products were
further confirmed by amplification with a set of interior primers.
All statistical analyses were based on the 2-tailed χ2
test, the Fisher exact test, or the Student t test.
A P value of less than .05 was considered statistically
Of 584 samples tested by culture, 19 (3.4%) were positive for B parapertussis and 39 (6.7%) for B pertussis. Of 564 samples tested by both culture and PCR, 15 had positive cultures
and 55 (9.4%) had positive PCRresults for B parapertussis, and 36 had positive cultures and 95 (16.3%) had positive PCR results
for B pertussis. Forty-four (86.3%) of 51 samples
with positive cultures for Bordetella also had positive
PCR results. In 11 specimens, B parapertussis and B pertussis DNA were simultaneously detected. Men and women
had similar culture and PCR positivity rates. Altogether, 153 subjects (26.2%)
were confirmed as harboring B pertussis (60.8%), B parapertussis (32.0%), or both (7.2%).
Of 564 subjects whose samples were tested by both culture and PCR, 198
(35.1%) had had paroxysmal cough for 7 days or less, and 366 (64.9%) had had
paroxysmal cough for more than 7 days at the time of sampling.
Of the 198 patients who had experienced paroxysmal cough for 7 days
or less, 24 (12.1%) had positive cultures or PCR results for B parapertussis and 35 (17.7%) had positive cultures or PCR results
for B pertussis. Of the 366 patients who had experienced
paroxysmal cough for more than 7 days, 32 (8.7%) had positive cultures or
PCR results for B parapertussis and 66 (18.0%) had
positive cultures or PCR results for B pertussis.
No statistically significant difference was found in positivity rates of culture
or PCR results for B pertussis (relative risk [RR],
0.98; 95% confidence interval [CI], 0.68-1.42; P=.99)
and for B parapertussis (RR, 1.39; 95% CI, 0.82-2.34; P=.26) between specimens taken from patients during the
first 7 days after the onset of paroxysmal cough and specimens taken during
the later course of illness.
Bordetella parapertussis and B pertussis were detected during 13 and 22 months of the surveillance
period and from samples sent by 17 and 23 health centers, respectively. Both B parapertussis and B pertussis
were detected during 11 months of the surveillance period and from samples
sent by 11 health centers (Figure 1).
At the time of sampling, no difference was found in the frequency of
whooping (11 [25%] of 44 vs 23 [26%] of 88; RR, 0.96; 95% CI, 0.52-1.79; P=.94), vomiting (19 [43%] of 44 vs 26 [30%] of 88; RR,
1.46; 95% CI, 0.91-2.33; P=.17), or mean duration
(in days) of paroxysmal cough at the time of sampling (15.2 [95% CI, 11.8-18.6]
vs 15.3 [95% CI, 12.7-17.6]; P =.95) between patients
with positive cultures or PCR results for B parapertussis and B pertussis. No difference was found
in the frequency of whooping (5 [19%] of 26 vs 6 [27%] of 22; RR, 0.71; 95%
CI, 0.25-2.0; P =.73) and vomiting (13 [50%] of 26
vs 12 [55%] of 22; RR, 0.92; 95% CI, 0.54-1.58;P=.98)
between patients younger than 7 years with positive cultures or PCR results
for B pertussis and B parapertussis, or in the frequency of whooping (6 [27%] of 22 vs 5 [23%] of 22;
RR, 1.20; 95% CI, 0.43-3.36; P >.99) and vomiting
(12 [55%] of 22 vs 7 [32%] of 22; RR, 1.70; 95% CI, 0.83-3.50; P=.22) between patients younger than 7 years and those aged 7 years
or older with positive cultures or PCR results for B parapertussis.
The positivity rate of laboratory-confirmed B parapertussis infection was highest in 2- to 6-year-olds, whereas the positivity
rate of B pertussis infection was highest in 7- to
15-year-olds (Figure 2). Bordetella pertussis infection was significantly more common than B parapertussis infection in schoolchildren and adults
(P<.001). The annual incidences of B pertussis and B parapertussis infections
were 5.9 and 3.4 cases per 100000, respectively. The annual incidences of B pertussis and B parapertussis
infections were 16.6 and 9.5 in children younger than 2 years, 19.6 and 20.5
in children aged 2 to 6 years, 27.2 and 15.1 in children aged 7 to 15 years,
and 1.5 and 0.2 in persons aged 16 years or older, respectively.
Based on the culture-proven cases reported by the official system, the
annual incidences of B pertussis infection in 1995
and 1996 were 1.3 and 0.6 per 100000 in southwestern Finland and 1.2 and 1.9
per 100000 in the whole country, respectively. In southwestern Finland, only
1 case of B parapertussi s infection was reported
during the surveillance period, and 3 cases were reported during the last
This study confirms that in an immunized population B pertussis and B parapertussis infections
remain common. Furthermore, B parapertussis infections
were more prevalent than usually documented, with one third of laboratory-confirmed Bordetella infections caused by B parapertussis. Bordetella parapertussis infection was as
common as B pertussis infection in children before
school entry, whereas in schoolchildren and adults B pertussis infection was markedly more prevalent. High rates of B pertussis infection in schoolchildren and adults confirm that protection
from B pertussis vaccinations decreases with time.
The sensitivity of B parapertussis PCR was
about 3 times higher than that of culture. The assay has been shown to be
specific by testing panels of bacterial species.14
Its specificity was also confirmed clinically in this study by the low positivity
rates obtained between infection peaks and in subjects 16 years and older.
The incidences of B pertussis and B parapertussis infections reported by the official reporting system,
based on patients with laboratory-confirmed infection, were lower than those
obtained from the enhanced surveillance. The enhanced surveillance clearly
supplemented the existing reporting system. Underdiagnosis of Bordetella infections is a more likely reason for the low incidences
reported by the official system than failure to report diagnosed cases.
The disease caused by B parapertussis is usually
milder than that caused by B pertussis.6-9,15Bordetella parapertussis infection can also be asymptomatic.11,15 Immunization can modify clinical
symptoms.12,16 Individuals with
mild symptoms due to these infections are not likely to be suspected of having
whooping cough and samples are not likely to be taken, suggesting that the
true prevalence of both infections may remain underestimated. Serological
surveys would most likely increase the incidence figures.14,16
Bordetella pertussis and B parapertussis can cause similar symptoms.6,8
In this outpatient population no difference was found in the frequency of
symptoms, such as whooping and vomiting, between patients with B pertussis and B parapertussis infections.
However, we could not exclude the possibility that the study was not large
enough to detect differences in symptom rates between those with B pertussis and B parapertussis infections.
Furthermore, the inclusion criteria may have biased the sample to include
only patients with severe symptoms. Duration of illness may differ, but we
did not have that information.
The protective role of B pertussis vaccination
against B parapertussis has been debated.4,10,17 Even experimental
animal studies have provided contradictory results.18,19
After B pertussis vaccination was introduced, incidences
of both infections markedly decreased in Denmark,4
whereas in the former Czechoslovakia peak B parapertussis morbidity remained the same in children younger than 7 years.10,16 Our results fall between the results
of these 2 studies, suggesting that B pertussis vaccine
may provide some protection against B parapertussis.
This partial protection would still allow natural infection to occur among
younger children. On the other hand, the B parapertussis immunity imparted by both B pertussis vaccinations
and infections might be more effective and longer lasting than B pertussis immunity based on vaccine alone, resulting in a low incidence
of B parapertussis infection in schoolchildren and
adults. In the development of less reactogenic acellular B pertussis vaccines, it may be important to estimate the protection
against B parapertussis infections provided by these