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Pertussis infection in infants and children: Clinical features and diagnosis

Authors: Sylvia Yeh, MD, ChrisAnna M Mink, MD


Section Editor: Morven S Edwards, MD
Deputy Editor: Mary M Torchia, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process
is complete.
Literature review current through: Jul 2018. | This topic last updated: Mar 30, 2018.

INTRODUCTION — The clinical presentation, including complications, and the diagnosis


of pertussis (whooping cough) infection in infants and children will be discussed here.
The treatment and prevention of pertussis in infants and children; the microbiology,
epidemiology, and pathogenesis of pertussis infection; and the clinical features,
treatment, and prevention of pertussis in adolescents and adults are discussed
separately:

● (See "Pertussis infection in infants and children: Treatment and prevention".)

● (See "Pertussis infection: Epidemiology, microbiology, and pathogenesis".)

● (See "Pertussis infection in adolescents and adults: Clinical manifestations and


diagnosis".)

● (See "Pertussis infection in adolescents and adults: Treatment and prevention".)

MICROBIOLOGY — Bordetella pertussis is a human pathogen with no known animal or


environmental reservoir. It is a fastidious gram-negative coccobacillus, surviving only a
few hours in respiratory secretions outside of the human body. Other Bordetella species,
including B. parapertussis, B. bronchiseptica, and B. holmesii, may cause a clinical
syndrome similar to whooping cough but are generally less severe. (See "Pertussis
infection: Epidemiology, microbiology, and pathogenesis", section on 'Microbiology'.)

Coinfection with other respiratory pathogens (eg, respiratory syncytial virus, adenovirus)
may occur [1-5].

EPIDEMIOLOGY

Incidence — Despite widespread vaccination, the incidence of pertussis has been rising


since the 1990s (figure 1), particularly in infants younger than one year (figure 2), who are
at the greatest risk of morbidity and mortality [6-9]. Atypical/mild and asymptomatic
infections are increasingly recognized in older children and adults but may be
underreported [10]. (See "Pertussis infection: Epidemiology, microbiology, and
pathogenesis", section on 'Epidemiology' and 'Complications' below.)
Although pertussis occurs year-round, the incidence appears to increase during the
summer and fall [11-13].

Transmission — Pertussis is spread by respiratory droplets, which are effectively


aerosolized by the paroxysms of coughing [14]. The risk of transmission is greatest
during the catarrhal stage [15].

When a case of pertussis is identified, exposed individuals should be notified and offered
preventive measures, if warranted. (See "Pertussis infection in infants and children:
Treatment and prevention", section on 'Postexposure prophylaxis' and "Pertussis
infection in adolescents and adults: Treatment and prevention", section on 'Postexposure
prophylaxis'.)

Incubation period — The average incubation period for B. pertussis is 7 to 10 days, with a


range of 6 to 20 days [16-18].

CLINICAL FEATURES — The clinical presentation of pertussis may vary with age and
immunity (from vaccination or natural infection).

Classic presentation — The classic presentation of pertussis includes paroxysms of


coughing, an inspiratory whoop, and posttussive vomiting. The classic presentation
typically occurs as a primary infection in unvaccinated children <10 years of age [10,19-
21], but it also may occur in vaccinated children and adults [22].

Classic pertussis ("the cough of 100 days") is divided into three stages:

● Catarrhal stage – The catarrhal stage appears similar to a viral upper respiratory
infection with mild cough and coryza. Fever is uncommon; if present, it is usually low
grade [23]. In contrast to that in a viral upper respiratory infection, the cough in
pertussis gradually increases instead of improving and the coryza remains watery
[19].

The catarrhal stage generally lasts one to two weeks [10].

● Paroxysmal stage – During the paroxysmal stage, coughing spells increase in


severity. The paroxysmal cough is distinctive: a long series of coughs between
which there is little or no inspiratory effort [19]. The child may gag, develop cyanosis,
and appear to be struggling for breath (movie 1). Sweating episodes may occur
between paroxysms. Paroxysms of coughing can develop spontaneously or be
precipitated by external stimuli. They are more bothersome at night. Complications
occur most frequently during the paroxysmal stage. (See 'Complications' below.)

The whoop, or noise made by the forced inspiratory effort that follows the coughing
attack (movie 2), is not always present (movie 3). In a prospective multicenter
surveillance study that included 2137 cases of B. pertussis among unvaccinated
patients, whooping occurred in 79 percent of children [23]. In a 2010 outbreak that
occurred predominantly in vaccinated children, whooping occurred in 22 to 44
percent; it was more frequent in children <1 year of age (44 percent) [24].

Posttussive vomiting is moderately sensitive and specific for pertussis in children. It


is more common in infants younger than 12 months than in older children. In a
systematic review and meta-analysis of six studies, posttussive vomiting had a
sensitivity of 60 percent (95% CI 40-77 percent) and a specificity of 66 percent (95%
CI 53-77 percent) for laboratory-confirmed pertussis in children [25].

The paroxysmal stage may last for two to eight weeks [10]. The coughing spells
increase in frequency during the first one to two weeks, remain at the same intensity
for two to three weeks, and decrease gradually thereafter.

● Convalescent stage – During the convalescent stage, the cough subsides over
several weeks to months. In a prospective multicenter surveillance study (in
predominantly unvaccinated children), the total duration of cough was >4 weeks in
62 percent and ≤4 weeks in 38 percent of 1548 patients with follow-up
questionnaires [23]. In another study of 62 children (5 to 16 years) with serologic
evidence of B. pertussis infection, the median duration of cough was 112 days
(range 38 to 191) [26].

Episodic coughing may recur or worsen during convalescence with interval upper
respiratory tract infections [10].

Atypical presentations — Atypical presentations of pertussis occur in young infants and


individuals who have been vaccinated [1,27]. They also may occur in unvaccinated
children [23,28,29]. The atypical features may vary with age and length of time elapsed
since the last vaccination (for vaccinated children). Atypical presentations may
contribute to the under-recognition of pertussis infection [10].

Infants — The clinical presentation of pertussis in young infants, particularly those


younger than four months of age, may include [1,19,30-36]:

● A short or absent catarrhal stage during which the infant can appear deceptively
well with no fever, watery coryza, sneezing, and a mild cough

● A paroxysmal stage characterized by gagging, gasping, eye bulging, vomiting,


cyanosis, and bradycardia (or tachycardia if illness is severe); the cough may or may
not be paroxysmal

● Complications, including apnea, seizures, respiratory distress, pneumonia and


pulmonary hypertension, hypotension/shock, renal failure, and death

● A close contact (usually a family member, often the mother or a sibling) with a
prolonged cough and no fever [30,37-41]
Pertussis infection in infants may be particularly severe, with increased rates of
hospitalization for complications including apnea, seizures, and pulmonary hypertension
[30,42-44]. The mortality rate in infants is approximately 1 percent [31,38,45,46]. (See
'Complications' below.)

Given the increased morbidity and mortality in infants, pertussis must be considered
early in the presentation of respiratory illness but is often difficult to distinguish from
other respiratory infections. In pertussis outbreaks, infants who required hospitalization
often presented to medical care at least once before pertussis was considered [30,33].

Clinical features that are more suggestive of pertussis than respiratory viruses in infants
<3 months of age were described in a case control study of 32 infants hospitalized with
pertussis and 92 control infants hospitalized with respiratory syncytial virus or influenza
[30]. Pertussis was associated with:

● Paroxysmal cough (approximately 90 versus 5 percent)

● Posttussive vomiting (approximately 40 versus 20 percent)

● Longer mean duration of symptoms (11 versus 3.4 days) and cough (10.7 versus 3.8
days) before admission

● Absence of fever (approximately 80 versus 50 percent)

● Decreased incidence of congestion (approximately 45 versus 85 percent)

● Cyanosis (approximately 65 versus 10 percent)

● Increased acute life-threatening event, apnea, or seizure (approximately 25 versus 5


percent)

● Higher mean white blood cell (WBC) count (20,700 versus 9900 cells/microL)

● Higher absolute lymphocyte count (13,300 versus 4900 lymphocytes/microL)

Vaccinated children — The clinical presentation and course of pertussis infection


generally are less severe in children who have been vaccinated [47-50].

The clinical features of pertussis infection in vaccinated and unvaccinated children were
described in a study of children who participated in a randomized trial comparing two
acellular pertussis vaccines with placebo [48]. All children were actively monitored for
pertussis infection until age six years. A total of 788 cases of laboratory-confirmed
pertussis were diagnosed. The following findings were noted:

● Vaccination decreased the median duration of pertussis-related cough throughout


the six year follow-up (number of days with two different pertussis vaccines versus
placebo group):
• 29 and 33 versus 61 days at 6 to 24 months of age

• 39 and 31 versus 60 days at 25 to 33 months of age

• 35 versus 52 days at 34 to 72 months

● Among children 6 to 24 months of age, vaccination also decreased the incidence of


pertussis-related apnea (47 and 36 percent versus 85 percent) and cyanosis (31 and
21 percent versus 65 percent)

The efficacy and effectiveness of pertussis vaccination in children are discussed


separately. (See "Diphtheria, tetanus, and pertussis immunization in children 6 weeks
through 6 years of age", section on 'Efficacy and effectiveness'.)

Older children and adolescents — Older children and adolescents with pertussis


infection may be asymptomatic or have a mild cough illness without any of the
characteristic features (ie, paroxysms, whoop, posttussive vomiting) [51-54]. Wheezing is
another atypical finding. In a 2010 statewide outbreak, wheezing was noted in 8 percent
of 501 children (mean age 8.4 years) with polymerase chain reaction-confirmed
pertussis [51].

Clinical features of pertussis in adolescents and adults are discussed separately. (See
"Pertussis infection in adolescents and adults: Clinical manifestations and diagnosis",
section on 'Clinical manifestations'.)

Laboratory findings — The predominant nonspecific laboratory indication of B. pertussis


infection is a leukocytosis resulting from lymphocytosis, although the WBC count may be
normal [18,55]. The absolute lymphocyte count is often ≥10,000 lymphocytes/microL
[30]. In a prospective multicenter surveillance study, 72 percent of patients with culture-
proven pertussis had leukocytosis (WBC count above the age-specific mean) and 76
percent had lymphocytosis (lymphocyte count above the age-specific mean) [23].
Clefting of the nuclei of white blood cells occurs occasionally in infants and young
children and may be a clue to the diagnosis [56-60].

In infants, the WBC count and lymphocyte count are directly correlated with disease
severity [31,34,61]. Marked leukocytosis (eg, >60,000 cells/microL) has been associated
with increased pertussis severity, including pertussis pneumonia and pulmonary
hypertension [61-64]. In a case series of infants <90 days who required intensive care for
treatment of pertussis, WBC ≥30,000 cells/microL at the time of presentation and rapid
rise of WBC to ≥30,000 cells/microL (mean five days after onset of cough) were
associated with increased severity and death [34]. (See 'Complications' below.)

Radiographic findings — In uncomplicated pertussis, chest radiographs may be normal


or demonstrate subtle abnormalities, such as peribronchial cuffing, perihilar infiltrates, or
atelectasis, but these findings are nonspecific.
Complications — The most common complications of pertussis infection include apnea,
pneumonia, and weight loss secondary to feeding difficulties and posttussive vomiting
[10,23]. These complications are more common in infants. Other complications include
seizures, encephalopathy, death, difficulty sleeping, pneumothorax, epistaxis,
subconjunctival hemorrhage, subdural hematoma, rectal prolapse, urinary incontinence,
and rib fracture [10,33,65-68].

In a multicenter surveillance study that included 2137 cases of culture confirmed


pertussis in unvaccinated outpatients (80 percent were <6 years), the overall
complication rate was 6 percent, but among infants younger than six months, the
complication rate was 24 percent [23]. In a retrospective cohort from a single institution,
complications occurred in 37 percent of infants younger than six months who were
hospitalized with pertussis [69]. Age <60 days, cough duration <7 days, history of color
change, parenteral intervention for apnea, and the need for oxygen in the emergency
department were associated with increased risk of complications.

● Apnea – Apnea occurs almost exclusively in infants, primarily those younger than
six months [23,24,45]. Apnea usually is associated with a paroxysm of coughing but
also occurs spontaneously, perhaps related to vagal stimulation [70,71]. In infants,
apnea may be the only manifestation of pertussis infection.

In a 2010 outbreak that included 968 cases of probable/confirmed pertussis, apnea


occurred in 26 percent of infants <6 months, 14 percent of infants 6 to 12 months,
and 8 percent of children 1 to 5 years [24].

● Pneumonia – Pneumonia (infection of the lung parenchyma) is one of the most


frequent complications of pertussis [23,33,42,45,46].

Primary B. pertussis pneumonia is associated with extreme leukocytosis (eg,


>60,000 cells/microL), pulmonary hypertension, and increased mortality, particularly
in young infants [31,62,72]. The pathologic findings of fatal B. pertussis infection
were evaluated in an autopsy study of 15 infants ≤4 months of age who had
polymerase chain reaction (PCR)- or culture-confirmed B. pertussis pneumonia; 12
of the infants had evidence of pulmonary hypertension [62]. Histopathologic
examination of respiratory tissue revealed evidence of necrotizing bronchiolitis,
intra-alveolar hemorrhage, and fibrinous edema. There were abundant leukocytes
and extracellular Bordetella in the cilia of the respiratory tract, and intracellular
bacteria and antigens in alveolar macrophages and ciliated epithelium. In a case-
control study designed to identify predictors of death in cases of fatal pertussis,
pneumonia more predictive of mortality than apnea [31].

● Seizures and encephalopathy – New-onset seizures occur in 1 to 2 percent of


infants and young children with pertussis [42,45,46]. The incidence of
encephalopathy is <1 percent. Pertussis appears to be associated with an increased
risk of epilepsy, but the absolute risk is low. In a population-based cohort in
Denmark, the 10-year cumulative incidence of epilepsy was 1.7 percent (95% CI 1.4-
2.1) among children with a hospital diagnosis of pertussis compared with 0.9
percent (95% CI 0.8-1.0) in the matched comparison group without pertussis [73].
(See "Seizures and epilepsy in children: Classification, etiology, and clinical features",
section on 'Etiology'.)

In a 2010 outbreak, seizures occurred in 2 of 51 children hospitalized with pertussis


(both young infants); one of the infants also had encephalopathy [24].

● Death – Most deaths from pertussis occur in infants younger than six months of
age, who are too young to have completed the primary series of pertussis vaccines
[33,38,45,46,74,75]. The case fatality rate for pertussis among infants younger than
six months of age is approximately 1 percent, with the majority of deaths occurring
in those younger than two months [31,38,45,46].

An association between epidemic pertussis and sudden infant death syndrome


(SIDS) has been suggested [76]. However, in a multicenter, case-control study to
investigate the relationship between pertussis infection and SIDS, pertussis PCR
was positive in 5.1 percent of cases and in 5.3 percent of controls [77]. Nonetheless,
it is plausible that fatal apnea occurring in an infant with undiagnosed pertussis
could present as SIDS. Laboratory testing for pertussis should be considered in
cases of apparent SIDS, particularly if the infant or other family members had been
coughing. (See "Sudden unexpected infant death including SIDS: Initial
management", section on 'Case investigation'.)

DIAGNOSIS

Clinical suspicion

Infants <4 months — Pertussis should be suspected (regardless of vaccination status


or wheezing) in infants <4 months with a cough illness, usually without significant fever
who have [19,26,36,51,78]:

● Cough that is not improving (of any duration); the cough may or may not be
paroxysmal

● Rhinorrhea in which the nasal discharge remains watery

● Apnea, seizures, cyanosis, vomiting, or poor weight gain

● Leukocytosis with lymphocytosis (white blood cell [WBC] count ≥20,000


cells/microL with ≥50 percent lymphocytes)

● Pneumonia

There should be a low threshold to suspect pertussis in young infants, given the risk of
serious complications. Clinical suspicion of pertussis in infants, especially those younger
than four months, should trigger immediate treatment. Laboratory confirmation should
not delay the initiation of treatment. Early diagnosis and prompt treatment, as well as
other precautionary measures, are essential to prevention of transmission. (See
'Complications' above and "Pertussis infection in infants and children: Treatment and
prevention".)

Hospitalization may be warranted because pertussis can progress rapidly in young


infants. Intensive care may be required, especially if apnea, cyanosis, or leukocytosis
>30,000 cells/microL (which is associated with significant morbidity) is present, given
the potential for rapid, unpredictable deterioration [36,79]. If the admitting hospital
cannot provide intensive care, transfer to a hospital with an intensive care unit may be
warranted [78].

Infants ≥4 months and children — Pertussis should be suspected (regardless of


vaccination status or wheezing) in infants ≥4 months and children with a cough illness,
usually without significant fever, who have [19,26,51,78]:

● Paroxysmal nonproductive cough of ≥7 days duration (with or without a whoop or


posttussive vomiting)

● A cough illness associated with rhinorrhea in which the nasal discharge remains
watery

● A cough illness with whoop, apnea, posttussive vomiting, subconjunctival


hemorrhage, or sleep disturbance

● Cyanosis

● Sweating episodes between paroxysms

The threshold of suspicion in contacts of young infants should be low, given the risk
of serious complications in young infants. Early diagnosis is essential to prevention
of transmission. (See 'Complications' above and "Pertussis infection in infants and
children: Treatment and prevention".)

Infants ≥4 months of age and children with suspected pertussis should be treated for
pertussis. Laboratory confirmation should not delay the initiation of treatment. (See
"Pertussis infection in infants and children: Treatment and prevention", section on
'Antimicrobial therapy'.)

Clinical diagnosis — Pertussis is a clinical diagnosis. Clinical case definitions of


pertussis may vary from country to country and depend upon the clinical scenario (eg,
outbreak setting, routine surveillance, determination of vaccine efficacy, etc) [19]. Most
clinical case definitions require two weeks of cough illness with at least one
characteristic feature of pertussis (paroxysms, whoop, posttussive vomiting).
We use the case definition provided by the Centers for Disease Control and Prevention
(CDC) (table 1) [8], which is similar to that provided by the World Health Organization
(WHO) [80].

According to the CDC case definition, pertussis can be diagnosed without laboratory
testing in patients who have a cough illness lasting ≥2 weeks without a more likely
diagnosis and at least one of the following symptoms (table 1) [8,19,80]:

● Paroxysms of coughing

● Inspiratory whoop

● Posttussive vomiting

● Apnea, with or without cyanosis (for infants <1 year only)

The diagnosis is confirmed if the patient has had contact with a laboratory-confirmed
case of pertussis and probable if the patient has not had such contact [8]. A probable
diagnosis of pertussis can also be made in infants <1 year who have acute cough illness
of any duration, at least one of the characteristic findings (paroxysm, whoop, posttussive
vomiting, apnea), and contact with a laboratory confirmed case. The sensitivity and
specificity of the WHO clinical case definition (which is similar to the CDC definition,
except that apnea is not a defining symptom) were evaluated in a study performed in Iran
where immunizations, health care, and transmission risks may be different than in other
countries [81]. Among 328 children 6 to 14 years of age who presented with ≥2 weeks of
cough, 6.4 percent had pertussis confirmed by polymerase chain reaction (PCR). When
only one of the characteristic findings (eg, paroxysms, whoop, posttussive vomiting) was
required, sensitivity and specificity were 95 and 15 percent, respectively. If two or more
characteristic symptoms were required for diagnosis, the sensitivity decreased to 81
percent and specificity increased to 60 percent. If all three characteristic symptoms were
required, sensitivity decreased to 10 percent and specificity increased to 91 percent.

Laboratory confirmation — Although laboratory testing is not necessary to make a


diagnosis of pertussis, we often perform it to confirm the diagnosis, particularly when
there is a need for contact prophylaxis. Laboratory testing also is beneficial for
confirming the diagnosis of pertussis in patients without an exposure history and for
public health considerations (eg, in an outbreak setting) [8,80]. However, laboratory
confirmation should not delay the initiation of treatment.

When indicated, laboratory testing should be performed as soon as the diagnosis of


pertussis is considered. B. pertussis is more difficult to grow/identify from specimens
obtained during or after the paroxysmal stage and after antibiotic therapy has been
initiated. Microbiologic studies that can confirm the diagnosis of pertussis include
bacterial culture, PCR, and serology [82]. The sensitivity and specificity of the tests vary
depending on age, time from symptom onset, vaccination history, and exposure history
(table 2) [10,52]. Among these tests, only culture and PCR meet criteria for laboratory
confirmation of a case for national reporting purposes [8]. Direct fluorescent antibody
testing can yield false positives and false negatives and should not be used to confirm
the diagnosis of pertussis [83].

We suggest the following approach to laboratory diagnosis of pertussis [19,84]:

● Cough <3 weeks duration

• Age <4 months – PCR and culture (if available) of nasopharyngeal specimens

False negatives may occur with culture, particularly if the specimen was not
adequate. False positives may occur with PCR – this may be due to specimens
being contaminated at the time of collection (eg, from environmental vaccine-
associated B. pertussis DNA), type of transport medium used, in-lab
contamination during specimen handling/processing, or if test validation
procedures have too low PCR thresholds [85-87].

• Age ≥4 months – PCR; serology (immunoglobulin G [IgG] to pertussis toxin [PT])


if ≥1 year since last pertussis vaccine and laboratory is able to provide cutoff
values in a validated assay for recent infection)

● Cough >3 weeks duration

• Age <4 months – PCR and culture (if available) of nasopharyngeal specimens
(serology is not useful)

• Age ≥4 months – Serology (IgG to PT) if ≥1 year since last pertussis vaccine
and laboratory is able to provide cutoff values in a validated assay for recent
infection)

The CDC provides information regarding best practices on the use of PCR for diagnosing
pertussis. These note that PCR may provide accurate results for up to four weeks after
cough onset [87]. After the fourth week of illness, diminishing DNA increases the risk of a
falsely-negative result. The PCR test also lacks sensitivity in previously immunized
people.

The diagnosis of pertussis is probable in infants <1 year who have acute cough illness of
any duration, at least one of the characteristic findings (paroxysm, whoop, posttussive
vomiting, apnea), and positive pertussis PCR [8].

The diagnosis of pertussis is confirmed in patient of any age with (table 1)


[8,19,26,80,88]:

● Acute cough illness of any duration and isolation of B. pertussis from a clinical
specimen
● Positive pertussis PCR who meets the clinical case definition (see 'Clinical
diagnosis' above)

● Anti-PT IgG titer ≥100 international units/mL or increase in anti-PT IgG titer, provided
that the patient did not receive pertussis vaccine in the previous year

Patients with discordant test results (eg, positive culture with negative PCR, negative
culture with positive PCR, or positive serology with negative PCR) should be presumed to
have pertussis.

Obtaining specimens — Nasopharyngeal specimens must be collected by swab or


aspiration from the ciliated respiratory epithelium of the posterior nasopharynx where B.
pertussis resides (picture 1). Aspiration is recommended [89], but supplies for aspiration
often are not readily available. Throat swabs and anterior nasal swabs have low rates of
recovery and should not be used for the diagnosis of pertussis.

Nasopharyngeal swabs for culture should be obtained with Dacron or calcium alginate
swabs with a flexible metal shaft. Cotton or rayon swabs contain fatty acids that are
toxic to B. pertussis. Nasopharyngeal swabs for PCR should be obtained with a polyester
(eg, Dacron), rayon, or nylon-flocked swabs. Cotton and calcium alginate may interfere
with PCR assays [87].

The patient or caregiver should be educated about the importance of a properly obtained
specimen and forewarned about the discomfort of the procedure. Proper specimen
collection typically induces cough or sneeze. The person obtaining the specimen should
wear gloves and a protective face mask.

The CDC has developed short videos describing the proper collection of nasopharyngeal
aspirate and swab specimens [90].

Disease reporting — Probable and confirmed cases of B. pertussis in the United States


(table 1) should be reported to public health authorities.

International outbreaks of pertussis should be reported to the appropriate local


authorities as well as to the World Health Organization regional office [80].

DIFFERENTIAL DIAGNOSIS

Infectious diseases — Other Bordetella species, such as B. parapertussis, B.


bronchiseptica, and B. holmesii may cause paroxysmal cough similar to whooping cough
[18,91-96]. These agents can be challenging for the laboratory to isolate and differentiate
from B. pertussis.

Other infectious agents that may cause illnesses with intractable coughing are listed
below and discussed separately [97]. Microbiologic testing generally differentiates these
infections from B. pertussis.
● Mycoplasma pneumoniae (see "Mycoplasma pneumoniae infection in children")

● Chlamydia spp (see "Chlamydia trachomatis infections in the newborn" and


"Pneumonia caused by Chlamydia species in children")

● Tuberculosis (see "Tuberculosis disease in children")

● Viral pathogens, including:

• Respiratory syncytial virus (see "Respiratory syncytial virus infection: Clinical


features and diagnosis")

• Adenovirus (see "Pathogenesis, epidemiology, and clinical manifestations of


adenovirus infection" and "Diagnosis, treatment, and prevention of adenovirus
infection")

• Parainfluenza viruses (see "Parainfluenza viruses in children")

• Influenza A and B viruses (see "Seasonal influenza in children: Clinical features


and diagnosis", section on 'Diagnosis')

• Rhinovirus (see "Epidemiology, clinical manifestations, and pathogenesis of


rhinovirus infections")

• Human metapneumovirus (see "Human metapneumovirus infections")

Some of these infections also may occur simultaneously with pertussis [1-5]. Thus,
the identification of another respiratory pathogen does not exclude the diagnosis of
pertussis.

Other conditions — Noninfectious processes to consider in the differential diagnosis of


infants and children with persistent cough are listed below and discussed separately.
Isolation or identification of B. pertussis through culture, polymerase chain reaction
(PCR) testing, or serology distinguishes pertussis from these conditions.

● Foreign body aspiration (see "Airway foreign bodies in children")

● Reactive airway disease/asthma (see "Wheezing phenotypes and prediction of


asthma in young children" and "Asthma in children younger than 12 years: Initial
evaluation and diagnosis")

● Allergic or infectious sinusitis (see "Allergic rhinitis: Clinical manifestations,


epidemiology, and diagnosis" and "Acute bacterial rhinosinusitis in children: Clinical
features and diagnosis")

● Gastroesophageal reflux (see "Gastroesophageal reflux in infants" and "Clinical


manifestations and diagnosis of gastroesophageal reflux disease in children and
adolescents")
● Aspiration pneumonia (see "Aspiration due to swallowing dysfunction in infants and
children")

Additional causes of chronic cough and the approach to the child with chronic cough are
discussed separately. (See "Causes of chronic cough in children" and "Approach to
chronic cough in children".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines


from selected countries and regions around the world are provided separately. (See
"Society guideline links: Pertussis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best
for patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you
to print or e-mail these topics to your patients. (You can also locate patient education
articles on a variety of subjects by searching on "patient info" and the keyword[s] of
interest.)

● Basics topics (see "Patient education: Whooping cough (The Basics)" and "Patient
education: Cough in children (The Basics)")

SUMMARY

● Despite widespread vaccination, the incidence of pertussis has been rising,


especially since the 1990s (figure 1), particularly in infants younger than one year
(figure 2). Pertussis is spread by respiratory droplets. The risk of transmission is
greatest during the catarrhal stage. The average incubation period is 7 to 10 days
(range 6 to 20 days). (See 'Epidemiology' above.)

● Classic pertussis typically occurs in unvaccinated children. It has three stages: a


catarrhal stage that lasts one to two weeks and is similar to an upper respiratory
infection; a paroxysmal stage that lasts two to eight weeks and is characterized by
paroxysms of coughing (movie 1), an inspiratory whoop (movie 2), and posttussive
vomiting; and a convalescent stage, during which the cough subsides over several
weeks to months. (See 'Classic presentation' above.)

● The presentation of pertussis in infants younger than four months may include (see
'Infants' above):
• A short, mild catarrhal stage during which the infant can appear deceptively well

• A paroxysmal stage characterized by gagging, gasping, eye bulging, vomiting,


cyanosis, and bradycardia (or tachycardia if illness is severe); the cough may or
may not be paroxysmal

• Complications, including apnea, seizures, respiratory distress, pneumonia and


pulmonary hypertension, hypotension/shock, renal failure, and death

• A close contact (usually a family member, often the mother) with a prolonged
cough

● Young children who have been vaccinated against pertussis usually have a milder
and shorter illness than unvaccinated children. Older children and adolescents with
pertussis infection may be asymptomatic or have a mild cough illness without any
characteristic features; they also may have wheezing. (See 'Vaccinated children'
above and 'Older children and adolescents' above.)

● The predominant laboratory findings of pertussis are nonspecific: leukocytosis and


lymphocytosis (eg, absolute lymphocyte count ≥10,000 lymphocytes/microL).
Marked leukocytosis (eg, >60,000 white blood cells/microL) has been associated
with increased pertussis severity. (See 'Laboratory findings' above.)

● Pertussis should be suspected (regardless of vaccination status or wheezing) in the


following patients (see 'Clinical suspicion' above):

• Infants <4 months with a cough illness, usually without significant fever, who
have:

- Cough that is not improving (of any duration); the cough may or may not be
paroxysmal (movie 1)

- Rhinorrhea in which the nasal discharge remains watery

- Apnea, seizures, cyanosis, vomiting, or poor weight gain

- Leukocytosis with lymphocytosis (white blood cell [WBC] count ≥20,000


cells/microL with ≥50 percent lymphocytes)

- Pneumonia

• Infants ≥4 months and children with a cough illness, usually without significant
fever who have:

- Paroxysmal nonproductive cough (movie 1 and movie 3) of ≥7 days'


duration (with or without a whoop or posttussive vomiting)
- A cough illness associated with rhinorrhea in which the nasal discharge
remains watery

- A cough illness with whoop (movie 2), apnea, posttussive vomiting,


subconjunctival hemorrhage, or sleep disturbance

- Cyanosis

- Sweating episodes between paroxysms

● Laboratory testing is beneficial for confirming the diagnosis of pertussis in patients


without an exposure history and for public health considerations (eg, in an outbreak
setting) (table 2). However, laboratory confirmation should not delay the initiation of
treatment. Hospitalization may be warranted for infants <4 months of age because
pertussis can progress rapidly in young infants. Intensive care may be required,
especially if there is apnea, cyanosis, or leukocytosis >30,000 cells/microL. (See
'Laboratory confirmation' above and "Pertussis infection in infants and children:
Treatment and prevention".)

● Probable and confirmed cases of pertussis in the United States (table 1) should be
reported to public health authorities. International outbreaks of pertussis should be
reported to the appropriate World Health Organization regional office [80]. (See
'Disease reporting' above.)

● The differential diagnosis of Bordetella pertussis infection includes infection with


other Bordetella species (eg, B. parapertussis, B. bronchiseptica, B. holmesii), other
respiratory pathogens (eg, Mycoplasma pneumoniae, Chlamydia, and respiratory
viruses). Microbiologic testing distinguishes these infections from B. pertussis. (See
'Infectious diseases' above.)

● Noninfectious conditions that should be considered in the differential diagnosis of


children with persistent or worsening cough include foreign body aspiration, reactive
airways disease/asthma, allergic or infectious sinusitis, gastroesophageal reflux,
and aspiration pneumonia. Isolation or identification of B. pertussis through culture,
polymerase chain reaction (PCR) testing, or serology distinguishes pertussis from
these conditions. (See 'Other conditions' above.)

REFERENCES

1. Crowcroft NS, Booy R, Harrison T, et al. Severe and unrecognised: pertussis in


UK infants. Arch Dis Child 2003; 88:802.
2. Abu Raya B, Bamberger E, Kassis I, et al. Bordetella pertussis infection
attenuates clinical course of acute bronchiolitis. Pediatr Infect Dis J 2013;
32:619.
3. Zouari A, Touati A, Smaoui H, et al. Dual infection with Bordetella pertussis and
Mycoplasma pneumoniae in three infants: case reports. Infection 2012; 40:213.
4. Nuolivirta K, Koponen P, He Q, et al. Bordetella pertussis infection is common in
nonvaccinated infants admitted for bronchiolitis. Pediatr Infect Dis J 2010;
29:1013.
5. Versteegh FG, Mooi-Kokenberg EA, Schellekens JF, Roord JJ. Bordetella
pertussis and mixed infections. Minerva Pediatr 2006; 58:131.
6. Edwards KM, Halasa N. Are pertussis fatalities in infants on the rise? What can
be done to prevent them? J Pediatr 2003; 143:552.
7. Kowalzik F, Barbosa AP, Fernandes VR, et al. Prospective multinational study of
pertussis infection in hospitalized infants and their household contacts. Pediatr
Infect Dis J 2007; 26:238.
8. Centers for Disease Control and Prevention. Pertussis (whooping cough). Survei
llance & Reporting. http://www.cdc.gov/pertussis/surv-reporting.html (Accesse
d on September 29, 2016).
9. Masseria C, Martin CK, Krishnarajah G, et al. Incidence and Burden of Pertussis
Among Infants Less Than 1 Year of Age. Pediatr Infect Dis J 2017; 36:e54.
10. Mattoo S, Cherry JD. Molecular pathogenesis, epidemiology, and clinical
manifestations of respiratory infections due to Bordetella pertussis and other
Bordetella subspecies. Clin Microbiol Rev 2005; 18:326.
11. Bhatti MM, Rucinski SL, Schwab JJ, et al. Eight-Year Review of Bordetella
pertussis Testing Reveals Seasonal Pattern in the United States. J Pediatric
Infect Dis Soc 2017; 6:91.
12. De Greeff SC, Dekkers AL, Teunis P, et al. Seasonal patterns in time series of
pertussis. Epidemiol Infect 2009; 137:1388.
13. Centers for Disease Control and Prevention. Pertussis. In: Epidemiology and Pre
vention of Vaccine-Preventable Diseases. The Pink Book: Course Textbook, 13th
ed, Hamborsky J, Kroger A, Wolfe S (Eds). Public Health Foundation, Washingto
n, DC 2015. www.cdc.gov/vaccines/pubs/pinkbook/index.html (Accessed on Ju
ne 03, 2015).
14. Warfel JM, Beren J, Merkel TJ. Airborne transmission of Bordetella pertussis. J
Infect Dis 2012; 206:902.
15. Cherry JD, Brunell PA, Golden GS, Karzon DT. Report of the Task Force on
Pertussis and Pertussis Immunization - 1988. Pediatrics 1988; 81:933.
16. Cherry JD. Epidemiological, clinical, and laboratory aspects of pertussis in
adults. Clin Infect Dis 1999; 28 Suppl 2:S112.
17. GORDON JE, HOOD RI. Whooping cough and its epidemiological anomalies. Am
J Med Sci 1951; 222:333.
18. Cherry JD, Heininger U. Pertussis and other Bordetella infections. In: Feigin and
Cherry’s Textbook of Pediatric Infectious Diseases, 8th ed, Cherry JD, Harrison
G, Kaplan SL, et al (Eds), Elsevier, Philadelphia 2018. p.1159.
19. Cherry JD, Tan T, Wirsing von König CH, et al. Clinical definitions of pertussis:
Summary of a Global Pertussis Initiative roundtable meeting, February 2011.
Clin Infect Dis 2012; 54:1756.
20. Cherry JD. Pertussis in the preantibiotic and prevaccine era, with emphasis on
adult pertussis. Clin Infect Dis 1999; 28 Suppl 2:S107.
21. Centers for Disease Control and Prevention (CDC). Pertussis outbreak in an
Amish community--Kent County, Delaware, September 2004-February 2005.
MMWR Morb Mortal Wkly Rep 2006; 55:817.
22. Cherry JD, Beer T, Chartrand SA, et al. Comparison of values of antibody to
Bordetella pertussis antigens in young German and American men. Clin Infect
Dis 1995; 20:1271.
23. Heininger U, Klich K, Stehr K, Cherry JD. Clinical findings in Bordetella pertussis
infections: results of a prospective multicenter surveillance study. Pediatrics
1997; 100:E10.
24. Chan MH, Ma L, Sidelinger D, et al. The California pertussis epidemic 2010: A
review of 986 pediatric case reports from San Diego county. J Pediatric Infect
Dis Soc 2012; 1:47.
25. Moore A, Ashdown HF, Shinkins B, et al. Clinical Characteristics of Pertussis-
Associated Cough in Adults and Children: A Diagnostic Systematic Review and
Meta-Analysis. Chest 2017; 152:353.
26. Harnden A, Grant C, Harrison T, et al. Whooping cough in school age children
with persistent cough: prospective cohort study in primary care. BMJ 2006;
333:174.
27. Hoppe JE. Neonatal pertussis. Pediatr Infect Dis J 2000; 19:244.
28. Heininger U, Cherry JD, Eckhardt T, et al. Clinical and laboratory diagnosis of
pertussis in the regions of a large vaccine efficacy trial in Germany. Pediatr
Infect Dis J 1993; 12:504.
29. Schläpfer G, Cherry JD, Heininger U, et al. Polymerase chain reaction
identification of Bordetella pertussis infections in vaccinees and family
members in a pertussis vaccine efficacy trial in Germany. Pediatr Infect Dis J
1995; 14:209.
30. Nieves DJ, Singh J, Ashouri N, et al. Clinical and laboratory features of pertussis
in infants at the onset of a California epidemic. J Pediatr 2011; 159:1044.
31. Mikelova LK, Halperin SA, Scheifele D, et al. Predictors of death in infants
hospitalized with pertussis: a case-control study of 16 pertussis deaths in
Canada. J Pediatr 2003; 143:576.
32. Izurieta HS, Kenyon TA, Strebel PM, et al. Risk factors for pertussis in young
infants during an outbreak in Chicago in 1993. Clin Infect Dis 1996; 22:503.
33. Winter K, Harriman K, Zipprich J, et al. California pertussis epidemic, 2010. J
Pediatr 2012; 161:1091.
34. Murray EL, Nieves D, Bradley JS, et al. Characteristics of severe Bordetella
pertussis infection among infants </= 90 days of age admitted to pediatric
intensive care units – Southern California, September 2009 - June 2011. J
Pediatric Infect Dis Soc 2013; 2:1.
35. Cherry JD. Pertussis in Young Infants Throughout the World. Clin Infect Dis
2016; 63:S119.
36. Cherry JD, Wendorf K, Bregman B, et al. An Observational Study of Severe
Pertussis in 100 Infants ≤120 Days of Age. Pediatr Infect Dis J 2018; 37:202.
37. Bisgard KM, Pascual FB, Ehresmann KR, et al. Infant pertussis: who was the
source? Pediatr Infect Dis J 2004; 23:985.
38. Tubiana S, Belchior E, Guillot S, et al. Monitoring the Impact of Vaccination on
Pertussis in Infants Using an Active Hospital-based Pediatric Surveillance
Network: Results from 17 Years' Experience, 1996-2012, France. Pediatr Infect
Dis J 2015; 34:814.
39. Skoff TH, Kenyon C, Cocoros N, et al. Sources of Infant Pertussis Infection in the
United States. Pediatrics 2015; 136:635.
40. Kara EO, Campbell H, Ribeiro S, et al. Survey of Household Contacts of Infants
With Laboratory-confirmed Pertussis Infection During a National Pertussis
Outbreak in England and Wales. Pediatr Infect Dis J 2017; 36:140.
41. Aquino-Andrade A, Martínez-Leyva G, Mérida-Vieyra J, et al. Real-Time
Polymerase Chain Reaction-Based Detection of Bordetella pertussis in Mexican
Infants and Their Contacts: A 3-Year Multicenter Study. J Pediatr 2017; 188:217.
42. Centers for Disease Control and Prevention (CDC). Pertussis--United States,
1997-2000. MMWR Morb Mortal Wkly Rep 2002; 51:73.
43. Marshall H, Clarke M, Rasiah K, et al. Predictors of disease severity in children
hospitalized for pertussis during an epidemic. Pediatr Infect Dis J 2015; 34:339.
44. Straney L, Schibler A, Ganeshalingham A, et al. Burden and Outcomes of Severe
Pertussis Infection in Critically Ill Infants. Pediatr Crit Care Med 2016; 17:735.
45. Halperin SA, Wang EE, Law B, et al. Epidemiological features of pertussis in
hospitalized patients in Canada, 1991-1997: report of the Immunization
Monitoring Program--Active (IMPACT). Clin Infect Dis 1999; 28:1238.
46. Centers for Disease Control and Prevention (CDC). Pertussis--United States,
2001-2003. MMWR Morb Mortal Wkly Rep 2005; 54:1283.
47. Bortolussi R, Miller B, Ledwith M, Halperin S. Clinical course of pertussis in
immunized children. Pediatr Infect Dis J 1995; 14:870.
48. Tozzi AE, Ravà L, Ciofi degli Atti ML, et al. Clinical presentation of pertussis in
unvaccinated and vaccinated children in the first six years of life. Pediatrics
2003; 112:1069.
49. Barlow RS, Reynolds LE, Cieslak PR, Sullivan AD. Vaccinated children and
adolescents with pertussis infections experience reduced illness severity and
duration, Oregon, 2010-2012. Clin Infect Dis 2014; 58:1523.
50. McNamara LA, Skoff T, Faulkner A, et al. Reduced Severity of Pertussis in
Persons With Age-Appropriate Pertussis Vaccination-United States, 2010-2012.
Clin Infect Dis 2017; 65:811.
51. Taylor ZW, Ackerson B, Bronstein DE, et al. Wheezing in children with pertussis
associated with delayed pertussis diagnosis. Pediatr Infect Dis J 2014; 33:351.
52. McIntyre PB, Sintchenko V. The "how" of polymerase chain reaction testing for
Bordetella pertussis depends on the "why". Clin Infect Dis 2013; 56:332.
53. Heininger U, Schmidt-Schläpfer G, Cherry JD, Stehr K. Clinical validation of a
polymerase chain reaction assay for the diagnosis of pertussis by comparison
with serology, culture, and symptoms during a large pertussis vaccine efficacy
trial. Pediatrics 2000; 105:E31.
54. Ward JI, Cherry JD, Chang SJ, et al. Bordetella Pertussis infections in vaccinated
and unvaccinated adolescents and adults, as assessed in a national prospective
randomized Acellular Pertussis Vaccine Trial (APERT). Clin Infect Dis 2006;
43:151.
55. Levene I, Wacogne I. Question 3. Is measurement of the lymphocyte count
useful in the investigation of suspected pertussis in infants? Arch Dis Child
2011; 96:1203.
56. Funaki T, Miyairi I. Lymphocytosis in a baby with pertussis. Lancet Infect Dis
2015; 15:130.
57. Pandey S, Cetin N. Peripheral smear clues for Bordetella pertussis. Blood 2013;
122:4012.
58. Kubic VL, Kubic PT, Brunning RD. The morphologic and immunophenotypic
assessment of the lymphocytosis accompanying Bordetella pertussis infection.
Am J Clin Pathol 1991; 95:809.
59. A 4-year-old girl with progressive cough and abnormal blood semar. Clin Infect
Dis 2017; 64:1629.
60. Meng QH, Shi W, Li LJ, Yao KH. "Cleaved Lymphocytes" Could Be Induced by
Pertussis Toxin Injection in Mice, and Are Actually Not Lymphocytes. Clin Infect
Dis 2018; 66:639.
61. Pierce C, Klein N, Peters M. Is leukocytosis a predictor of mortality in severe
pertussis infection? Intensive Care Med 2000; 26:1512.
62. Paddock CD, Sanden GN, Cherry JD, et al. Pathology and pathogenesis of fatal
Bordetella pertussis infection in infants. Clin Infect Dis 2008; 47:328.
63. Donoso A, León J, Ramírez M, et al. Pertussis and fatal pulmonary hypertension:
a discouraged entity. Scand J Infect Dis 2005; 37:145.
64. Halasa NB, Barr FE, Johnson JE, Edwards KM. Fatal pulmonary hypertension
associated with pertussis in infants: does extracorporeal membrane
oxygenation have a role? Pediatrics 2003; 112:1274.
65. Tiwari T, Murphy TV, Moran J, National Immunization Program, CDC.
Recommended antimicrobial agents for the treatment and postexposure
prophylaxis of pertussis: 2005 CDC Guidelines. MMWR Recomm Rep 2005;
54:1.
66. Mark A, Granström M. Impact of pertussis on the afflicted child and family.
Pediatr Infect Dis J 1992; 11:554.
67. Watts CC, Acosta C. Pertussis and bilateral subdural hematomas. Am J Dis
Child 1969; 118:518.
68. Greenberg DP, von König CH, Heininger U. Health burden of pertussis in infants
and children. Pediatr Infect Dis J 2005; 24:S39.
69. Wallace SS, Cruz AT, Quinonez RA, Caviness AC. Risk factors for complications
in hospitalized young infants presenting with uncomplicated pertussis. Hosp
Pediatr 2011; 1:16.
70. Vincent JM, Wack RP, Person DA, Bass JW. Pertussis as the cause of recurrent
bradycardia in a young infant. Pediatr Infect Dis J 1991; 10:340.
71. Surridge J, Segedin ER, Grant CC. Pertussis requiring intensive care. Arch Dis
Child 2007; 92:970.
72. Sawal M, Cohen M, Irazuzta JE, et al. Fulminant pertussis: a multi-center study
with new insights into the clinico-pathological mechanisms. Pediatr Pulmonol
2009; 44:970.
73. Olsen M, Thygesen SK, Østergaard JR, et al. Hospital-Diagnosed Pertussis
Infection in Children and Long-term Risk of Epilepsy. JAMA 2015; 314:1844.
74. Haberling DL, Holman RC, Paddock CD, Murphy TV. Infant and maternal risk
factors for pertussis-related infant mortality in the United States, 1999 to 2004.
Pediatr Infect Dis J 2009; 28:194.
75. Winter K, Zipprich J, Harriman K, et al. Risk Factors Associated With Infant
Deaths From Pertussis: A Case-Control Study. Clin Infect Dis 2015; 61:1099.
76. Lindgren C, Milerad J, Lagercrantz H. Sudden infant death and prevalence of
whooping cough in the Swedish and Norwegian communities. Eur J Pediatr
1997; 156:405.
77. Heininger U, Kleemann WJ, Cherry JD, Sudden Infant Death Syndrome Study
Group. A controlled study of the relationship between Bordetella pertussis
infections and sudden unexpected deaths among German infants. Pediatrics
2004; 114:e9.
78. Cherry JD, Harrison R, Bradley JS, et al. Pertussis in young infants -- Guidance fo
r clinicians. May 2010, updated June 2011. www.cdph.ca.gov/HealthInfo/discon
d/Pages/Pertussis.aspx (Accessed on July 10, 2015).
79. American Academy of Pediatrics. Pertussis in young infants. www.aap-ca.org/cl
inical/pertussis/pertussis_in_young_infants.html (Accessed on February 14, 20
12).
80. World Health Organization. WHO-recommended surveillance standard of pertus
sis. http://www.who.int/immunization/monitoring_surveillance/burden/vpd/sur
veillance_type/passive/pertussis_standards/en/ (Accessed on October 17, 201
4).
81. Ghanaie RM, Karimi A, Sadeghi H, et al. Sensitivity and specificity of the World
Health Organization pertussis clinical case definition. Int J Infect Dis 2010;
14:e1072.
82. Centers for Disease Control and Prevention. Pertussis (Whooping Cough). Diagn
osis Confirmation. http://www.cdc.gov/pertussis/clinical/diagnostic-testing/dia
gnosis-confirmation.html.
83. Faulkner, A, Skoff T, Martin S, et al. Pertussis. In: VPD Surveillance Manual, 5th E
dition, 2011. http://www.cdc.gov/vaccines/pubs/surv-manual/index.html (Acce
ssed on December 10, 2014).
84. Tapiainen T, Aittoniemi J, Immonen J, et al. Finnish guidelines for the treatment
of community-acquired pneumonia and pertussis in children. Acta Paediatr
2016; 105:39.
85. Centers for Disease Control and Prevention (CDC). Outbreaks of respiratory
illness mistakenly attributed to pertussis--New Hampshire, Massachusetts, and
Tennessee, 2004-2006. MMWR Morb Mortal Wkly Rep 2007; 56:837.
86. Mandal S, Tatti KM, Woods-Stout D, et al. Pertussis Pseudo-outbreak linked to
specimens contaminated by Bordetella pertussis DNA From clinic surfaces.
Pediatrics 2012; 129:e424.
87. Centers for Disease Control and Prevention. Best practices for health care profe
ssionals on the use of polymerase chain reaction (PCR) for diagnosing pertussi
s. http://www.cdc.gov/pertussis/clinical/diagnostic-testing/diagnosis-pcr-bestp
ractices.html (Accessed on October 17, 2014).
88. Wang K, Harnden A. Pertussis-induced cough. Pulm Pharmacol Ther 2011;
24:304.
89. Centers for Disease control and Prevention. Guidelines for the Control of Pertus
sis Outbreaks. CDC: Atlanta, GA, 2000. http://www.cdc.gov/vaccines/pubs/pert
ussis-guide/guide.htm.
90. Centers for Disease Control and Prevention. Pertussis (whooping cough). Speci
men collection. www.cdc.gov/pertussis/clinical/diagnostic-testing/specimen-c
ollection.html (Accessed on October 02, 2014).
91. Waters V, Halperin S. Bordetella pertussis. In: Mandell, Douglas, and Bennett's Pr
inciples and Practice of Infectious Diseases, 7th, Mandell GL, Bennett JE, Dolin
R (Eds), Elsevier, Churchill, Livingstone, Philadelphia 2009. p.2955.
92. Rodgers L, Martin SW, Cohn A, et al. Epidemiologic and laboratory features of a
large outbreak of pertussis-like illnesses associated with cocirculating
Bordetella holmesii and Bordetella pertussis--Ohio, 2010-2011. Clin Infect Dis
2013; 56:322.
93. Kamiya H, Otsuka N, Ando Y, et al. Transmission of Bordetella holmesii during
pertussis outbreak, Japan. Emerg Infect Dis 2012; 18:1166.
94. Spicer KB, Salamon D, Cummins C, et al. Occurrence of 3 Bordetella species
during an outbreak of cough illness in Ohio: epidemiology, clinical features,
laboratory findings and antimicrobial susceptibility. Pediatr Infect Dis J 2014;
33:e162.
95. Koepke R, Bartholomew ML, Eickhoff JC, et al. Widespread Bordetella
parapertussis Infections-Wisconsin, 2011-2012: Clinical and Epidemiologic
Features and Antibiotic Use for Treatment and Prevention. Clin Infect Dis 2015;
61:1421.
96. Heininger U, Schlassa D. Two Distinct Episodes Of Whooping Cough Caused By
Consecutive Bordetella Pertussis And Bordetella Parapertussis Infections In A
Fully Immunized Healthy Boy. Pediatr Infect Dis J 2016; 35:1275.
97. Wirsing von König CH, Rott H, Bogaerts H, Schmitt HJ. A serologic study of
organisms possibly associated with pertussis-like coughing. Pediatr Infect Dis J
1998; 17:645.

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