Clinical Manifestations of Bordetella pertussis Infection in ...

Clinical Manifestations of Bordetella pertussis Infection in ...

Clinical Manifestations of Bordetella

pertussis Infection in Immunized

Children and Young Adults*

Einat Yaari, MD; Yael Yafe-Zimerman, MD; Shepard B. Schwartz, MD;

Paul E. Slater, MD, MPH; Pesach Shvartzman, MD; Nachum Andoren, PhD;

David Branski, MD; and Eitan Kerem, MD

Study objectives: The incidence and prevalence of pertussis in adults have increased in recent

years. It has been shown that previously immunized adults and adolescents are the main sources

of transmission of Bordetella pertussis. The aim of this study was to describe the clinical

presentation and the clinical course of pertussis in children and young adults who were

immunized previously against B pertussis.

Design: Retrospective study.

Subjects: Children and young adults who were reported by local physicians to the Department of

Epidemiology in the Israeli Ministry of Health with serologically confirmed pertussis and who

were immunized previously were included. Information sought included personal data, epidemiologic

data, signs and symptoms, laboratory results, initial diagnosis, and treatment.

Results: In the 95 previously immunized patients with serologically confirmed pertussis (mean

age [� SD], 8.9 � 4.4 years old; range, 5 to 30 years old), the mean duration from onset of

symptoms until the final diagnosis of pertussis was 23 � 15 days. The disease was usually atypical

and generally mild. All the described patients had cough, usually prolonged, lasting 4 � 3.6

weeks. Only 6% had the classic whoop. The mean WBC count was 8.7 � 2.6 cells/mm 6 , and the

lymphocyte count was 40 � 12%. Two patients were admitted to the hospital for severe

pneumonia. Among the reported cases, the proportion of patients between the ages of 10 and 45

years increased from 6.5% during the period from 1971 to 1980, to 26% during the period from

1980 to 1990, and to 38% during a 1989 outbreak.

Conclusions: Pertussis in previously immunized individuals is usually characterized by an atypical

and relatively mild clinical course. Patients suffer mainly from a prolonged and persistent cough.

Early diagnosis may lead to prompt administration of therapy. Prophylaxis of exposed persons

might be effective in decreasing both severity and transmission of the disease.

(CHEST 1999; 115:1254–1258)

Key words: pertussis, clinical course; pertussis, epidemiology; pertussis, immunization

Pertussis is an acute disease of the respiratory tract

caused by Bordetella pertussis and characterized

by progressive, repetitive, and paroxysmal coughing.

It is regarded as a vaccine-preventable childhood

illness. Classic pertussis lasts for 6 to 8 weeks, and it

*From the Department of Pediatrics (Drs. Yaari, Yafe-Zimerman,

Schwartz, Branski, and Kerem) and Unit of Pediatric Respiratory

Medicine (Dr. Kerem), Shaare Zedek Medical Center, Jerusalem,

Israel; Department of Epidemiology (Dr. Slater), Israel

Ministry of Health, Jerusalem, Israel; Department of Family

Medicine (Dr. Shvartzman), Faculty of Health Sciences, Ben

Gurion University of the Negev, Beer Sheva, Israel; and Government

Central Laboratories (Dr. Andoren), Israel Ministry of

Health, Jerusalem, Israel.

Manuscript received May 12, 1998; revision accepted December

3, 1998.

Correspondence to: Eitan Kerem, MD, Pediatric Respiratory

Medicine, Shaare Zedek Medical Center, PO Box 3235, Jerusalem

91031, Israel; e-mail:

may be divided into three stages of clinical illness:

catarrhal, paroxysmal, and convalescent. Whooping

cough, cyanotic spells, and brief apnea episodes may

also occur. Leukocytosis (20,000 to 100,000 cells/�L)

with absolute lymphocytosis is characteristic. A

chronic cough may persist for several months. 1 Since

the introduction of routine childhood immunization,

pertussis morbidity and mortality have declined

markedly. 2 However, despite widespread vaccination,

the disease was not eradicated, and an increased

incidence rate has been reported in the last

2 decades. 3 Cases have been reported primarily in

nonimmunized or underimmunized populations, 3,4

although outbreaks in well-immunized populations

have also occurred. Several reports of pertussis

outbreaks have been documented recently among

older children and young adults who were previously

1254 Clinical Investigations

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immunized by vaccination. 5–10 Furthermore, the incidence

and prevalence of pertussis in adults are far

higher than previously reported. 11–15 Investigations

of outbreaks have documented that adults develop

infection with B pertussis and transmit the organism

to susceptible children or other adults. Thus, previously

immunized adults and adolescents are the main

sources of transmission of B pertussis. 15,16

The period of immunity induced by the pertussis

vaccine tends to wane within 5 to 10 years and is

shorter than that induced by the disease itself. 17

Although the number of susceptible adults is increasing,

it is difficult to determine the true incidence of

pertussis in adults. Studies of adults with prolonged

cough have found that 20 to 25% have serologic

evidence of recent pertussis infection. 11–14,18–20

However, adults may have an atypical presentation

of pertussis with a modified clinical course. 18–20

Because the signs and symptoms are usually nonspecific,

pertussis is rarely considered in adults. This

may lead to underdiagnosis and lack of, or a delay in,

treatment. Furthermore, in vaccinated populations,

adults maintain the ability to transmit B pertussis and

are now the primary source of infection to susceptible

children who may develop severe disease. Several

studies on a small number of adult patients with

pertussis reported the association between pertussis

and chronic cough. However, to the best of our

knowledge, the disease in previously immunized

children and adults was documented in a limited

number of patients. Therefore, the aim of this study

was to investigate the clinical presentation and the

course of the disease in previously immunized patients

suffering from B pertussis infection.

Materials and Methods

Data regarding pertussis cases were obtained from the reports

of local physicians of the Israel Ministry of Health. In Israel,

physicians are required to report all cases of pertussis. Retrospectively,

we analyzed all serologically confirmed cases between the

years of 1986 and 1991 among individuals between the ages of 5

and 30 years old whose medical records were accessible.

In all cases, the Pertussis Laboratory of the Ministry of Health

Central Laboratories confirmed the diagnosis of pertussis. For

the purpose of this study, serologic confirmation of pertussis

required an agglutination titer � 1:640, or a fourfold rise in

agglutination titers obtained 2 to 3 weeks apart, or positive

pertussis IgM levels determined by enzyme-linked immunosorbent

assay method. 21 As cutoff, negative, and positive control, we

used in-house standards calibrated by using a pertussis kit

(Virotech GmbH; Russelsheim, Germany). Cultures were not


The reporting physicians were contacted and asked to complete

a questionnaire based on the patient’s medical records.

Information sought included personal data, epidemiologic data,

signs and symptoms, laboratory results, initial diagnosis, treatment,

and complications.

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Since 1956, when pertussis immunization was first

introduced in Israel, the number of yearly cases has

declined from � 10,000 in 1955 to � 100 in 1996

(data reported by Israel Ministry of Health). Nonetheless,

outbreaks of pertussis were reported between

1980 and 1990. 9

Of the 1,091 cases reported between the years

1971 and 1980, the percentage of cases in the group

aged 10 to 45 years was 6.5%. This figure increased

during the next decade to 26% of the 754 reported

cases. In 1989, 38% of the 219 reported cases

occurred among individuals between the ages of 10

and 45 years.

Of the 552 cases of pertussis reported to the

Ministry of Health from January 1986 to December

1991, 283 were children and young adults between

the ages of 5 and 30 years (mean age, 10.4 � 4.3

years old; median, 10 years old). Only 180 patients

completed pertussis vaccination during childhood

(63%). Clinical information was available for 95

individuals (39% were male) aged 5 to 30 years

(mean age, 8.9 � 4.4 years old; median, 9 years old).

Seventy patients were 5 to 10 years old, 16 were 11

to 14 years old, and 9 were 15 to 30 years old. In 66%

of these 95 patients, a history of contact with other

individuals with pertussis was documented.

The mean duration from onset of symptoms until

the final diagnosis of pertussis was 23 � 15 days

(range, 7 to 90 days; median, 14 days). In 46% of the

cases, pertussis was the initial diagnosis; most of the

patients who developed the disease were diagnosed

in a small kibbutz community during a pertussis

outbreak after the diagnosis of a first case. Various

incorrect diagnoses were ascribed until the diagnosis

of pertussis was established. Mycoplasma pneumoniae

infection was the most common initial diagnosis

(17%). Other initial diagnoses included sinusitis

(7%), upper respiratory tract infection (4%),

asthma (4%), laryngitis (3%), and suspected cystic

fibrosis (1%).

Table 1 shows the frequency of symptoms in the

95 vaccinated patients with serologically confirmed

pertussis. The disease in these patients was atypical,

because the clinical course was generally mild. All

the described patients had cough, usually prolonged,

lasting 4 � 3.6 weeks (range, 1 to 24 weeks; median

3 weeks). The cough was productive in 7% of the

patients, whereas the rest had a dry cough; only 6%

had the classic whoop. Of the patients, 13% had

temperature � 37.5°C. Five of the patients visited

an emergency department due to severe cough and

dyspnea. Two required hospitalization: a 5-year-old

girl with hypoxemia and a 10-year-old boy who

CHEST / 115 /5/MAY, 1999 1255

Table 1—Rate of Symptoms of Pertussis Among

Previously Immunized Patients (n � 95)

Symptoms % of Patients

Cough 100

Dry cough 93

Paroxysmal nocturnal cough 21

Posttussive vomiting 13

Fever 13

Productive cough 7

Wheezing 7

Apnea 7

Whoop 6

Cyanosis 3

Hoarseness 2

developed secondary pneumonia with a small pleural

effusion (pleurocentesis was not performed).

CBC count was taken in 63 patients (66%). The

mean WBC count was 8,700 � 2,600/mm 3 (range,

3,950 to 24,500/mm 3 ; median, 8,600/mm 3 ), and the

lymphocyte count was 40 � 12% (range, 10 to 68%;

median, 38%). A chest radiograph was performed on

41 patients (42%) and disclosed abnormalities in 8

(20%). Four radiographs showed enhanced interstitial

markings, two revealed bilateral perihilar shadows,

one showed a right lower lobe infiltrate with a

small amount of pleural effusion that could not be

tapped, and one showed a right middle lobe infiltrate.

Sixty-eight patients (71%) received antibiotic therapy

before the diagnosis of pertussis was made. The

majority (78% of treated patients) received erythromycin,

while others were treated with penicillin,

amoxicillin, or doxycycline. In most patients there

was no apparent clinical improvement with antibiotic



In this study, the clinical presentation of pertussis

in previously immunized children and young adults

was found to be relatively mild yet protracted. The

three typical stages of pertussis were absent. All

patients had a prolonged cough that lasted for

several weeks. The classic whooping cough was

found in only a few patients, and lymphocytosis was

generally absent. Thus, besides the long duration of

cough, there may be no typical symptoms and signs

that would alert the physician to consider the diagnosis

of pertussis. Therefore, a heightened index of

suspicion needs to be maintained. Considering the

highly contagious potential of B pertussis, the history

should be evaluated carefully to search for the

presence of contacts suffering from similar symp-

toms. Many patients in our study were diagnosed in

a small community during a pertussis outbreak after

the diagnosis of the first case in an infant. Pertussis is

rarely considered in adults until a child contact

develops classic symptoms of the disease. 22 Long et

al 23 underscored this fact in their study of the silent

transmission of pertussis in families. Fifty percent of

the contacts of pertussis had serologic evidence of a

recent infection. Many had onset of illness before

that of the index case. Most of the actual primary

cases were � 14 years old. Thus, adults are the most

important source of pertussis infection in the community.

Pertussis is much more common in adults than

previously believed. In Israel, the proportion of

adolescents and young adults among the reported

pertussis cases increased dramatically from 6.5%

from 1971 to 1980 to 26% from 1980 to 1990 and

38% during the 1989 outbreak. This trend is similar

to that reported by the Centers for Disease Control

and Prevention in the United States, 24 which found

that the proportion of pertussis cases occurring in

patients � 10 years old increased from 15% from

1977 to 1978 to 28% during the time from 1992 to

1994. Before the vaccination era, the majority of

pertussis cases occurred among infants. At that time,

most of the population was exposed to pertussis and

acquired natural immunity during the first years of

life. Subsequent exposure to other infants and young

children with pertussis served to boost immunity.

However, the immunity induced by the whole-cell

vaccination is shorter than the immunity induced by

the disease itself, and tends to wane within 5 to 10

years. 17 Thus, several decades after the introduction

of the pertussis vaccine, many adults became susceptible

to pertussis. Although the vaccine has been very

effective in controlling the disease, the transmission

of B pertussis has not been eliminated by vaccination

and still causes morbidity, even in the vaccinated

population. 25 The 1993 pertussis outbreak in Cincinnati

6 occurred primarily among immunized children,

demonstrating that the vaccine did not give full

protection against the disease. It is now appreciated

that adults are a major reservoir for the spread of the

infection to infants. 15,16,20 Pertussis was also isolated

from adults infected with HIV who complained of

persistent cough. 26

Yet, many physicians are unaware that adults may

themselves develop pertussis. 27 This, in addition to

the nonspecific or relative lack of symptoms among

adults with pertussis, has led to under-recognition of

the disease in this age category. 18

The only typical finding of pertussis in our study

was a prolonged and disturbing cough that lasted

from several weeks to several months. Only 5% had

whoop. Similarly, Wright et al 12 reported that cough

1256 Clinical Investigations

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was found in � 85% of the immunized adults with

pertussis. Whoop and lymphocytosis were not observed.

Prospective studies suggested that 20 to 25%

of adults with persistent cough might have pertussis.

3,19 Therefore, epidemiologic studies are needed

to determine the incidence of pertussis in adults with

respiratory illness.

In our study, the duration of time until the final

diagnosis was 23 � 15 days. This delay in diagnosis

may be critical, because initiation of therapy after

3 weeks will not shorten the course of the disease

or prevent its spread. 28 Early diagnosis of pertussis

relies on clinical suspicion, and the definitive

diagnosis of pertussis relies on laboratory tests.

Cultures are difficult to obtain and need to be

taken early in the course of the disease. 29 The

percentage of positive cultures changes precipitously

from 67 to 81% shortly after exposure to

25%, 14%, and 0% during the 3rd, 4th, and 5th

weeks, respectively. Compared with cultures, direct

fluorescent antigen detection is not more

sensitive, and it is much less specific. Determination

of antibody titer IgA and IgG to lymphocytosis

promoting factor, filamentous hemagglutinin, and

agglutinogens (antibodies against various virulent

factors of B pertussis) is currently the most sensitive

diagnostic test. 29,30 Polymerase chain reaction,

using a specific probe for B pertussis, may offer an

early diagnosis of pertussis with high specificity

and sensitivity. 31–33

Pertussis in immunized children and young adults

may be associated with morbidity. Five percent of

the patients in our study visited an emergency

department, and 2% were hospitalized. In addition,

many patients had unnecessary and costly diagnostic

evaluations and may have suffered from anxiety

because of the undiagnosed chronic and protracted

cough. Patients may experience loss of time from

work or school due to the persistent cough of

pertussis. Although the clinical presentation in immunized

children and young adults is atypical and

the course is usually benign, as shown in our study,

pertussis may still cause morbidity.

In conclusion, pertussis should be considered in

the differential diagnosis of persistent cough in

previously immunized children and adults. Given the

relative unavailability of accurate diagnostic tests and

the usual absence of whoop or lymphocytosis, a

recommendation for prompt administration of erythromycin

in patients presenting with persistent cough

and the prophylaxis of exposed persons before culture

or serologic results are available should be

considered. This would be effective in decreasing

both disease severity and transmission of B pertussis.

34 Because pertussis is not a life-threatening

illness in adults, pertussis vaccination is not currently

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recommended in persons � 6 years of age. However,

the availability of the less reactogenic acellular vaccine

may allow booster immunization and should be

thoughtfully considered.


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