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Fiona P. Havers, MD, MHS; Pedro L. Moro, MD, MPH; Susan Hariri, PhD; and Tami Skoff, MS 

Pertussis, or whooping cough, is an acute infectious disease 

caused by the bacterium Bordetella pertussis. Outbreaks of 

pertussis were first described in the 16th century by Guillaume 

de Baillou. The organism was first isolated by Jules Bordet and 

Octave Gengou in 1906. 

In the 20th century, pertussis was one of the most common 

childhood diseases and a major cause of childhood mortality 

in the United States. Before the availability of pertussis vaccine 

in the 1940s, more than 200,000 cases of pertussis were 

reported annually. Since widespread use of the vaccine began, 

incidence has decreased more than 75% compared with the 

prevaccine era. 

Pertussis remains a major health problem among children 

worldwide. Data from a recent modeling study suggest that 

more than 24 million new pertussis cases occurred globally 

among children younger than age 5 years in 2014 and caused 

an estimated 160,700 deaths. 

Bordetella pertussis 

B. pertussis is a small, aerobic gram-negative rod. It requires 

special media for isolation. 

B. pertussis produces multiple antigenic and biologically 

active products, including pertussis toxin (PT), filamentous 

hemagglutinin (FHA), agglutinogens, adenylate cyclase, 

pertactin, and tracheal cytotoxin. These products are 

responsible for the clinical features of pertussis disease. An 

immune response to one or more of these products produces 

immunity following infection. Immunity following B. pertussis 

infection is not permanent. 

Pathogenesis 

Pertussis is primarily a toxin-mediated disease. The bacteria 

attach to the cilia of the respiratory epithelial cells, produce 

toxins that paralyze the cilia, and cause inflammation of 

the respiratory tract, which interferes with the clearing of 

pulmonary secretions. Pertussis antigens appear to allow the 

organism to evade host defenses in that lymphocytosis is 

promoted but chemotaxis is impaired. 

Previously it was thought that B. pertussis did not invade the 

tissues. However, studies have shown the bacteria to be present 

in alveolar macrophages. 

Pertussis 

● Acute infectious disease caused 

by Bordetella pertussis 

● Outbreaks first described in 

16th century 

● Bordetella pertussis isolated 

in 1906 

● More than 200,000 cases 

annually in the United States 

in prevaccine era 

Bordetella pertussis 

● Aerobic gram-negative bacteria 

● Antigenic and biologically 

active components: 

■ Pertussis toxin (PT) 

■ Filamentous hemagglutinin 

(FHA) 

■ Agglutinogens 

■ Adenylate cyclase 

■ Pertactin 

■ Tracheal cytotoxin 

Pertussis Pathogenesis 

● Primarily a toxin-mediated 

disease 

● Bacteria attach to cilia of 

respiratory epithelial cells 

● Toxins cause inflammation 

which interferes with clearance 

of pulmonary secretions 

● Pertussis antigens allow evasion 

of host defenses 
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Pertussis Clinical Features 

● Incubation period 7 through 10 

days (range, 4 through 21 days) 

● Catarrhal stage: Insidious onset, 

similar to the common cold 

■ 1-2 weeks 

● Paroxysmal stage: More 

severe cough and may 

experience paroxysms of 

numerous, rapid coughs 

■ 1-6 weeks 

● Convalescence stage: 

Gradual recovery 

■ weeks to months 

Clinical Features 

The incubation period of pertussis is commonly 7 through 10 

days, with a range of 4 through 21 days. The clinical course of 

the illness is divided into three stages: catarrhal, paroxysmal, 

and convalescent. 

The first stage, the catarrhal stage, is characterized by the 

insidious onset of coryza (runny nose), sneezing, low-grade 

fever, and a mild, occasional cough similar to the common 

cold. The cough gradually becomes more severe and after 1 

to 2 weeks, the second, or paroxysmal, stage, begins. Fever is 

generally minimal throughout the course of the illness. 

It is during the paroxysmal stage that the diagnosis of 

pertussis is usually suspected. Characteristically, the patient 

might have bursts, or paroxysms, of numerous, rapid coughs, 

apparently due to difficulty expelling thick mucus from the 

tracheobronchial tree. At the end of the paroxysm, a long 

inspiratory effort is usually accompanied by a characteristic 

high-pitched whoop. During such an attack, the patient may 

become cyanotic. Children and young infants, especially, 

might appear very ill and distressed. Vomiting and exhaustion 

might follow the episode. The person does not appear to be ill 

between attacks. 

Paroxysmal attacks generally occur more frequently at night, 

with an average of 15 attacks per 24 hours. During the first 1 or 

2 weeks of this paroxysmal stage, the attacks might increase in 

frequency, remain at the same level for 2 to 3 weeks, and then 

gradually decrease. The paroxysmal stage usually lasts 1 to 6 

weeks but may persist for up to 10 weeks. Infants younger than 

age 6 months may not have the strength to have a whoop, but 

they can have paroxysms of coughing. Additionally, the classic 

whoop might not be present in persons with milder disease. 

In the convalescent stage, recovery is gradual. The cough 

becomes less paroxysmal and disappears in 2 to 3 weeks. 

However, paroxysms often recur with subsequent respiratory 

infections for many months after the onset of pertussis. 

Adolescents, adults, and children who were previously 

vaccinated may become infected with B. pertussis but may 

have milder disease than infants and young children. Pertussis 

infection in these persons may be asymptomatic or present 

as illness ranging from a mild cough illness to classic pertussis 

with persistent cough (i.e., lasting more than 7 days). Inspiratory 

whoop is not common. 

Even though the disease may be milder in older persons, 

those who are infected may still transmit the disease to other 

susceptible persons, including unimmunized or incompletely 

immunized infants. An adult, adolescent, or older school-age 
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child is often found to be the first case in a household with 

multiple pertussis cases and is often the source of infection for 

young infants. 

Complications 

The most common complication, and the cause of most 

pertussis-related deaths, is secondary bacterial pneumonia. 

Young infants are at highest risk for developing pertussisassociated complications. Data from 2000–2017 indicate that 

pneumonia occurred in 13.2% of all reported pertussis cases, 

and among 18.6% of infants younger than age 6 months. 

Neurologic complications such as seizures and encephalopathy 

may occur as a result of hypoxia from coughing, or possibly 

from pertussis toxin. Neurologic complications of pertussis are 

more common among infants. 

Other less serious complications of pertussis include otitis 

media, anorexia, and dehydration. Complications resulting from 

pressure effects of severe paroxysms include pneumothorax, 

epistaxis, subdural hematomas, hernias, and rectal prolapse. 

Between 2000 and 2017, 307 deaths from pertussis were 

reported to CDC; children younger than age 2 months 

accounted for 84.0% of these deaths. During the same time 

period, among infants, the annual mean number of pertussis 

cases, hospitalizations, and deaths were 2,957 (range 1,803 

to 4,994), 1,122 (range 544 to 1,938), and 15 (range 3 to 35), 

respectively. 

Adolescents and adults may also develop complications of 

pertussis, such as difficulty sleeping, urinary incontinence, 

pneumonia, rib fracture, syncope, and weight loss. 

Laboratory Testing 

The diagnosis of pertussis is based on a clinical history of signs 

and symptoms, as well as a variety of laboratory tests (e.g., 

culture, polymerase chain reaction [PCR], and serology). 

Culture is considered the gold standard laboratory test and is 

the most specific of the laboratory tests for pertussis. However, 

fastidious growth requirements make B. pertussis difficult 

to culture. The yield of culture can be affected by specimen 

collection, transportation, and isolation techniques. Specimens 

from the posterior nasopharynx, not the throat, should be 

obtained using polyester, rayon, nylon, or calcium alginate 

(not cotton) swabs. Isolation rates are highest during the first 2 

weeks of illness (catarrhal and early paroxysmal stages). Cultures 

are less likely to be positive if performed later in the course of 

illness (more than 2 weeks after cough onset) or on specimens 

from persons who have received antibiotics or who have been 

Pertussis Complications 

● Most common complication 

and cause of death is secondary 

bacterial pneumonia 

● Young infants at highest risk 

● Neurologic complications— 

seizures, encephalopathy 

● Less serious complications— 

otitis media, anorexia, 

dehydration 

● 307 deaths between 2000 

and 2017 
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vaccinated. Since adolescents and adults have often been 

coughing for several weeks before they seek medical attention, 

it is often too late for culture to be useful. 

PCR is a rapid test and has excellent sensitivity. PCR tests vary 

in specificity, so obtaining culture confirmation of pertussis for 

at least one possible case is recommended any time there is 

suspicion of a pertussis outbreak. Results should be interpreted 

along with the clinical symptoms and epidemiological 

information. PCR should be performed on nasopharyngeal 

specimens taken at 0 to 3 weeks following cough onset but may 

provide accurate results for up to 4 weeks of cough in infants 

or unvaccinated persons. After the fourth week of cough, the 

amount of bacterial DNA rapidly diminishes, which increases the 

risk of obtaining false negative results. PCR assay protocols that 

include multiple targets allow for Bordetella speciation. False 

positive results may be obtained because of contamination in 

the laboratory or during specimen collection. Direct comparison 

with culture is necessary for validation, and the use of multiple 

targets is recommended to distinguish B. pertussis from other 

Bordetella species. 

Serologic testing is generally more useful for diagnosing 

pertussis during the later phase of disease when both culture 

and PCR are likely to be negative. For the CDC/FDA single-point 

serologic assay, the optimal timing for specimen collection is 

2 to 8 weeks following cough onset, when the antibody titers 

are at their highest. However, serology may be performed on 

specimens collected up to 12 weeks following cough onset. 

Many state public health labs have included this assay as part of 

their testing regimen for pertussis. 

Commercially, there are many different serologic tests used in 

the United States with unproven or unknown clinical accuracy. 

CDC is actively engaged in better understanding the usefulness 

of these commercially available assays. 

Because direct fluorescent antibody testing of nasopharyngeal 

secretions has been demonstrated in some studies to have low 

sensitivity and variable specificity, such testing should not be 

relied on as a criterion for laboratory confirmation. 

An elevated white blood cell count with a lymphocytosis 

is usually present in classical pertussis among infants. The 

absolute lymphocyte count often reaches 20,000 or greater. 

However, there may be no lymphocytosis in some infants and 

children or in persons with mild or modified cases of pertussis. 

Medical Management 

The medical management of pertussis patients is primarily 

supportive, although antibiotics are of some value if 

administered early. This therapy eradicates the organism from 

secretions, thereby decreasing communicability and may 
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modify the course of the illness if initiated early (i.e., during the 

first 1 to 2 weeks of cough before coughing paroxysms begin). 

Recommended antibiotics are azithromycin, clarithromycin, and 

erythromycin. Trimethoprim-sulfamethoxazole can also be used. 

Preventive Measures 

Immunity following pertussis is not permanent. Unvaccinated 

or incompletely vaccinated persons recovering from pertussis 

should begin or complete active immunization with DTaP or 

Tdap as indicated. 

Vaccination history of close contacts of pertussis patients should 

also be assessed. An antibiotic effective against pertussis should 

be administered to all close contacts of persons with pertussis, 

regardless of age and vaccination status. All close contacts 

younger than age 7 years who have not completed the 3-dose 

primary vaccination series of a pertussis-containing vaccine and 

the first booster dose usually given at age 15 through 18 months 

should complete the series according to the minimum intervals. 

Close contacts who are age 4 through 6 years and who have not 

yet received the second booster dose of pertussis-containing 

vaccine (usually the fifth dose of DTaP [diphtheria and tetanus 

toxoids and acellular pertussis vaccine]) should be vaccinated. 

Epidemiology 

Occurrence 

Pertussis occurs worldwide. 

Reservoir 

Pertussis is a human disease. No animal or insect source 

or vector is known to exist. Adolescents, adults, and older 

school-age children are an important reservoir for B. pertussis 

and are often the source of infection for infants. 

Transmission 

Transmission most commonly occurs person-to-person 

through contact with respiratory droplets, or by contact with 

airborne droplets of respiratory secretions. Transmission occurs 

less frequently by contact with an infected person’s freshly 

contaminated articles. 

Temporal Pattern 

Pertussis has no distinct seasonal pattern, but it may increase in 

the summer and fall. 

Communicability 

Pertussis is highly communicable, as evidenced by secondary 

attack rates of 80% among susceptible household contacts. 

Persons with pertussis are infectious from the beginning of 

Pertussis Epidemiology 

● Reservoir 

■ Humans 

● Transmission 

■ Person-to-person through 

respiratory droplets or 

contact with airborne 

droplets 

■ Exposure to fomites 

● Temporal pattern 

■ No distinct seasonal pattern, 

but may increase in the 

summer and fall 

● Communicability 

■ Highly communicable 

■ Infectious from catarrhal 

stage through third week 

of paroxysms 
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Pertussis Secular Trends 

in the United States 

● Average of 175,000 cases per 

year before vaccine 

● Cases gradually declined after 

vaccine introduced in 1940s 

● Between 1980 and 1990, 2,900 

reported cases per year 

● Incidence gradually increasing 

in United States since late 1980s 

with large epidemic peaks since 

mid-2000s 

■ Waning of vaccine-induced 

immunity may play a role 

in increase 

the catarrhal stage through the third week after the onset 

of paroxysms or until 5 days after the start of effective 

antimicrobial treatment. 

Secular Trends in the United States 

Before the availability of vaccine, pertussis was a common cause 

of morbidity and mortality among children. During the 6-year 

period from 1940 through 1945, more than 1 million cases of 

pertussis were reported, an average of 175,000 cases per year 

(approximately 150 cases per 100,000 population). 

Following introduction of whole-cell pertussis vaccine in 

the 1940s, pertussis incidence gradually declined, reaching 

15,000 reported cases in 1960 (approximately 8 per 100,000 

population). By 1970, annual incidence was fewer than 5,000 

cases per year and, between 1980 and 1990, an average of 2,900 

cases per year were reported (approximately 1 per 100,000 

population). 

Reported pertussis incidence has been gradually increasing 

in the United States since the late 1980s and early 1990s, and 

large epidemic peaks in disease have been observed since the 

mid-2000s. A total of 48,277 pertussis cases were reported in 

2012, the largest number reported since the mid-1950s. There 

are likely many factors contributing to the observed increase in 

reported disease. These include changes in diagnostic testing, 

heightened recognition and reporting of pertussis cases, 

and molecular changes in the organism. However, waning 

of vaccine-induced immunity is thought to play a key role in 

countries, including the United States, that have transitioned to 

acellular vaccines in the 1990s. 

Infants younger than age 1 year continue to have the highest 

rates of pertussis. In 2018, pertussis incidence per 100,000 was 

72.3 in infants younger than age 6 months and 32.7 in infants 

age 6 to 12 months, compared to 1.4 in persons age 20 years 

or older. However, the epidemiology of pertussis has changed 

since the late 1980s, and an increasing burden of reported 

cases in the United States is now occurring among fully 

vaccinated children and adolescents. Between 2000–2006, the 

second highest average annual incidence rate was reported 

among adolescents age 11 through 18 years (13.1 per 100,000 

population). Between 2007 and 2014, children age 7 through 

10 years had the second highest average annual incidence 

rate (28.3 cases per 100,000 population). While the incidence 

of pertussis in children age 7 through 10 years and 11 through 

18 years was comparable between 2015 and 2016, the rate 

of disease in adolescents age 11 through 18 years once again 

surpassed the rates of disease among children age 7 through 

10 years during this period. The observed changes in pertussis 

epidemiology in recent years coincide with the transition to 
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acellular vaccines in the United States and the aging of the 

first acellular-primed birth cohorts, suggesting a key role of 

waning immunity. 

Among children born during 2016–2017, 93.3% had received 

at least 3 doses of DTaP vaccine by age 24 months, and 80.6% 

had received at least 4 doses of DTaP vaccine by age 24 months. 

Although Tdap coverage among adolescents age 13 through 

17 years reached 90.2% in 2019, coverage remains low among 

adults (31.7% in 2017). 

Pertussis-containing Vaccines 

Whole-cell pertussis vaccines were first licensed in the 

United States in 1914 and were available as a combined 

vaccine with diphtheria and tetanus toxoids (as DTP) in 1948. 

Based on controlled efficacy trials conducted in the 1940s 

and on subsequent observational efficacy studies, a series of 

4 doses of whole-cell DTP vaccine was 70% to 90% effective 

in preventing serious pertussis disease. Local reactions such 

as redness, swelling, and pain at the injection site occurred 

following up to 50% of doses of whole-cell DTP vaccines. 

Fever and other mild systemic events were also common. 

Concerns about safety led to the development of more 

purified (acellular) pertussis vaccines, which are associated 

with a lower frequency of adverse reactions. No DTP vaccines 

are currently licensed in the United States. 

Acellular pertussis vaccine is combined with tetanus toxoid 

and diphtheria toxoid as DTaP (Infanrix and Daptacel) or Tdap 

(Boostrix and Adacel). DTaP and Tdap contain the same pertussis 

components, but Tdap contains a reduced quantity of some 

pertussis antigens and diphtheria toxoid. Boostrix contains a 

reduced quantity of tetanus toxoid compared to Infanrix. 

Children younger than age 7 years should receive DTaP 

vaccine or DT vaccine (in instances where the pertussis vaccine 

component is contraindicated or where the physician decides 

that pertussis vaccine is not to be administered). Persons age 

7 years or older should receive the Td vaccine or Tdap vaccine 

(Tdap would be off-label for children age 7 through 9 years, but 

is still recommended by ACIP), even if they have not completed 

a series of DTaP or DT. Tdap (Boostrix) is approved for persons 

age 10 years or older; Tdap (Adacel) is approved for persons age 

10 through 64 years. 

There are five combination vaccines that contain DTaP vaccine. 

DTaP-HepB-IPV (Pediarix) is licensed for the first 3 doses of 

the DTaP series among children age 6 weeks through 6 years. 

DTaP-IPV/Hib (Pentacel) is licensed for the first 4 doses of the 

component vaccines among children age 6 weeks through 4 

years. DTaP-IPV (Kinrix) is licensed only for the fifth dose of DTaP 

and fourth dose of IPV among children age 4 through 6 years. 

Pertussis-containing Vaccines 

● DTaP (Daptacel and Infanrix) 

● Tdap (Adacel and Boostrix) 

● DTaP-HepB-IPV (Pediarix) 

● DTaP-IPV/Hib (Pentacel) 

● DTaP-IPV (Kinrix and Quadracel) 

● DTaP-IPV-Hib-HepB (Vaxelis) 
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Pertussis-containing 

Vaccine Characteristics 

● Administered by intramuscular 

injection 

● Contains aluminum as 

an adjuvant 

Pertussis-containing 

Vaccination Schedule 

● DTaP 

■ 3-dose primary series at age 

2, 4, and 6 months 

■ Primary series interval of 

4- to 8-weeks and minimum 

interval 4 weeks 

■ Boosters at age 15 through 

18 months and age 4 

through 6 years 

■ Minimum interval for dose 4 

is 6 months from dose 3 and 

minimum age is 12 months 

■ If dose 4 is given on or after 

4th birthday, the 5th dose 

is optional 

■ DT is used in place of 

DTaP if child has a valid 

contraindication to 

pertussis vaccine 

DTaP-IPV (Quadracel) is licensed only for the fifth dose of DTaP 

and fourth or fifth dose of IPV among children age 4 through 6 

years. DTaP-IPV-Hib-HepB (Vaxelis) is licensed for use in children 

age 6 weeks through 4 years. 

Characteristics 

Pertussis vaccines are administered by intramuscular injection. 

Each dose of pertussis-containing vaccine contains aluminum 

as an adjuvant but no preservative. DTaP-HepB-IPV (Pediarix), 

DTaP-IPV/Hib (Pentacel), DTaP-IPV-Hib-HepB (Vaxelis), DTaP-IPV 

(Kinrix), and DTaP-IPV (Quadracel) contain neomycin and 

polymyxin B as antibiotics. DTaP-IPV-Hib-HepB (Vaxelis) contains 

streptomycin as an antibiotic. DTaP-HepB-IPV (Pediarix) and 

DTaP-IPV-Hib-HepB (Vaxelis) vaccines contain yeast protein. 

Presentations of some pertussis-containing vaccines contain 

latex rubber. 

Vaccination Schedule and Use 

DTaP (Infanrix and Daptacel) 

DTaP (diphtheria, tetanus toxoids, and acellular pertussis 

vaccine) is recommended for children age 6 weeks through 

6 years. The routine schedule is a primary series of 3 doses at 

age 2, 4, and 6 months, a booster dose between age 15 through 

18 months, and another booster dose between age 4 through 

6 years (total of 5 doses). The first 3 doses should be given at 

4- to 8-week intervals (minimum of 4 weeks). Dose 4 should 

follow dose 3 by no less than 6 months and should not be 

administered before age 12 months. 

Dose 4 of both brands of DTaP is recommended to be 

administered at age 15 through 18 months (15 through 

20 months for Daptacel). Dose 4 may be given as early as age 

12 months if at least 6 months have elapsed since dose 

3 and, in the opinion of the vaccine provider, the child is 

unlikely to return for an additional visit between age 15 

through 18 months. 

Children who received 4 doses before their fourth birthday 

should receive a fifth dose of DTaP before entering school. The 

fifth dose is not necessary (but may be given) if dose 4 in the 

series was given on or after the fourth birthday. Administering 

the fifth dose increases antibody levels and may decrease the 

risk of school-age children transmitting the disease to younger 

siblings who are not fully vaccinated. 

If a child has a valid contraindication to pertussis vaccine, DT 

should be used to complete the vaccination series. If the child 

was younger than age 12 months when the first dose of DT 

was administered (as DTP, DTaP, or DT), the child should receive 

a total of 4 DT doses. If the child was age 12 months or older 

at the time the first dose of DT was administered, 3 doses 
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(with dose 3 administered 6 through 12 months after dose 2) 

will complete the primary DT series. If dose 4 of DTP, DTaP, or 

DT is administered before the fourth birthday, a fifth dose is 

recommended at age 4 through 6 years. 

DTaP-HepB-IPV (Pediarix) 

DTaP-HepB-IPV vaccine is approved for use as a 3-dose series 

for children age 6 weeks through 6 years. It is administered to 

infants at age 2, 4, and 6 months. The minimum intervals for 

DTaP-HepB-IPV vaccine are determined by the DTaP component. 

The 3 doses must be separated by at least 4 weeks between 

doses. Because the minimum age for the first dose of DTaP-

HepB-IPV vaccine is 6 weeks, this vaccine cannot be used for 

the birth dose of hepatitis B (HepB) vaccine. The final dose of 

DTaP-HepB-IPV vaccine should be administered at age 24 weeks 

or older, the minimum age for completion of the hepatitis B 

vaccine series. When DTaP-HepB-IPV vaccine is used to provide 

3 doses at age 2, 4, and 6 months (based on the DTaP and IPV 

schedules), this will result in a 4-dose HepB vaccine series, which 

is acceptable. 

DTaP-IPV/Hib (Pentacel) 

DTaP-IPV/Hib vaccine is approved for use as a 4-dose series 

for children age 6 weeks through 4 years. It is administered to 

infants at age 2, 4, 6, and 15 through 18 months. The minimum 

intervals for DTaP-IPV/Hib vaccine are determined by the 

DTaP component. The first 3 doses must be separated by at 

least 4 weeks between doses. Dose 4 must be separated from 

dose 3 by at least 6 months, and should not be administered 

before age 12 months. When DTaP-IPV/Hib vaccine is used 

to provide 4 doses at age 2, 4, 6, and between 15 through 18 

months (based on the DTaP and Hib schedules), an additional 

booster dose with IPV-stand alone or DTaP-IPV vaccine should 

be administered at age 4 through 6 years. This will result in a 

5-dose IPV vaccine series, which is acceptable. 

DTaP-IPV-Hib-HepB (Vaxelis) 

DTaP-IPV-Hib-HepB is approved for use as a 3-dose series 

for children age 6 weeks through 4 years. It is administered 

to infants at age 2, 4, and 6 months. The minimum intervals 

for DTaP-IPV-Hib-HepB vaccine are determined by the DTaP 

component. The 3 doses must be separated by at least 4 weeks 

between doses. Because the minimum age for the first dose of 

DTaP-IPV-Hib-HepB vaccine is 6 weeks, this vaccine cannot be 

used for the birth dose of hepatitis B (HepB) vaccine. The final 

dose of DTaP-IPV-Hib-HepB vaccine should be administered at 

age 24 weeks or older, the minimum age for completion of the 

hepatitis B vaccine series. When DTaP-IPV-Hib-HepB vaccine is 

used to provide 3 doses at age 2, 4, and 6 months (based on 

the DTaP and IPV schedules), this will result in a 4-dose HepB 

vaccine series, which is acceptable. 
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Pertussis-containing 

Vaccination Schedule 

● Tdap 

■ 1 dose at age 11 through 18 

for adolescents who have 

completed DTaP series 

■ Booster dose of Td or Tdap 

every 10 years for all persons 

DTaP-IPV (Kinrix) 

DTaP-IPV (Kinrix) vaccine is approved only for dose 5 of DTaP 

vaccine and dose 4 of IPV vaccine in children age 4 through 

6 years whose previous DTaP vaccine doses have been with 

Infanrix and/or Pediarix for dose 1, 2, and 3 and Infanrix for 

dose 4. However, if DTaP-IPV (Kinrix) vaccine is administered to 

children who received another brand of DTaP vaccine for prior 

DTaP vaccine doses, or if administered as dose 1, 2, 3, or 4 of the 

DTaP vaccine series or dose 1, 2, or 3 of the IPV vaccine series, 

the dose of DTaP-IPV (Kinrix) does not need to be repeated. 

DTaP-IPV (Quadracel) 

DTaP-IPV (Quadracel) vaccine is approved only for dose 5 of 

DTaP vaccine and dose 4 or 5 of IPV vaccine in children age 4 

through 6 years who have received 4 doses of Pentacel and/or 

Daptacel vaccine. However, if DTaP-IPV (Quadracel) vaccine is 

administered to children who received another brand of DTaP 

vaccine for prior DTaP vaccines doses, or if administered as 

dose 1, 2, 3, or 4 of the DTaP vaccine series or dose 1, 2, or 3 of 

the IPV series, the dose of DTaP-IPV (Quadracel) does not need 

to be repeated. 

Tdap (Boostrix and Adacel) and Td (Tenivac and Tdvax) 

Both Tdap vaccines are approved by the FDA for a booster dose 

for persons who have completed the recommended childhood 

DTP/DTaP vaccination series. Boostrix is approved for persons 

age 10 years or older. Adacel is approved for a single dose in 

persons age 10 through 64 years. A second dose of Adacel is 

also licensed for administration 8 or more years after the first 

Tdap dose and for use for tetanus prophylaxis when indicated 

for wound management if at least 5 years have elapsed since 

the previous receipt of any tetanus toxoid-containing vaccine. 

A single Tdap dose is recommended for adolescents age 11 

through 18 years who have completed the recommended 

childhood DTP/DTaP vaccination series, preferably at age 11 

through 12 years. Adults age 19 years or older who have not 

previously received Tdap should receive a single dose of Tdap. 

To reduce the burden of pertussis in infants, a dose of Tdap 

has been recommended during each pregnancy since 2012, 

although this practice is an off-label use. 

All adolescents and adults should have received a primary 

series of at least 3 documented doses of tetanus and diphtheria 

toxoids-containing vaccine (i.e., DTaP, DTP, DT, or Td) during their 

lifetime. A person without such documentation should receive 

a series of 3 doses of tetanus- and diphtheria-containing 

vaccine. One of these doses, preferably the first, should be Tdap. 

The remaining 2 doses should be either Td or Tdap. 
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For persons age 7 to 9 years who receive a dose of Tdap as 

part of the catch-up series, an adolescent Tdap dose should 

be administered at age 11 through 12 years. If a Tdap dose is 

administered at age 10 years or older, the Tdap dose may count 

as the adolescent Tdap dose. Either brand of Tdap may be used. 

Adults age 19 years or older who previously have not received 

Tdap should receive a single dose of Tdap to protect against 

pertussis and reduce the likelihood of transmission. For adults 

age 19 through 64 years, either brand of Tdap may be used. 

Adults age 65 years or older should be vaccinated with Boostrix, 

if feasible. However, either vaccine administered to a person age 

65 years or older is immunogenic and would provide protection. 

A dose of either vaccine would be considered valid. 

Adolescents and adults who have not previously received 

Tdap, and have or anticipate having close contact with an 

infant younger than age 12 months (e.g., parents, siblings, 

grandparents, child care providers, and health care personnel) 

should receive a single dose of Tdap to protect against pertussis. 

Ideally, these persons should receive Tdap at least 2 weeks 

before beginning close contact with the infant. 

Health care personnel should receive a single dose of Tdap 

as soon as feasible if they have not previously received Tdap, 

regardless of the time since their most recent Td vaccination. 

When Tdap is indicated (e.g., routine vaccination, catch-up 

vaccination, or pregnancy), it can be administered regardless 

of the interval since the last tetanus- or diphtheria-toxoidcontaining vaccine. After receipt of Tdap, persons should 

continue to receive a dose of Td or Tdap for routine booster 

immunization against tetanus and diphtheria every 10 years 

unless needed sooner for tetanus prophylaxis as part of wound 

management. 

Vaccination during Pregnancy 

To reduce the burden of pertussis in infants, health care 

providers should administer a dose of Tdap during each 

pregnancy, regardless of the mother’s prior Tdap vaccination 

history, although this is an off-label use. To maximize the 

maternal antibody response and passive antibody transfer to 

the infant, optimal timing for Tdap administration is between 

27 and 36 weeks of gestation, preferably during the earlier 

part of this period, although Tdap may be administered at any 

time during pregnancy. For women not previously vaccinated 

with Tdap, if Tdap is not administered during pregnancy, Tdap 

should be administered immediately postpartum. Tdap should 

be administered during each pregnancy (preferred) or during 

the postpartum period regardless of the interval since the last 

tetanus- or diphtheria toxoid-containing vaccine. 

Use of Tdap 

● 1 dose Tdap during each 

pregnancy (off-label use) 

● 1 dose Tdap for the 

following with no previous 

documentation of Tdap: adults, 

adolescents and adults who 

have or anticipate having close 

contact with an infant younger 

than age 12 months, and health 

care personnel 

● 3 doses of tetanus- and 

diphtheria-containing vaccine 

(1 dose should be Tdap) for 

adolescents and adults 

without documentation of 

a primary series 
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Pertussis-containing 

Vaccine Efficacy 

● DTaP vaccine efficacy 80%-85% 

● Tdap similar efficacy 

Pertussis-containing Vaccine 

Contraindications and Precautions 

● Contraindication 

■ Severe allergic reaction 

to vaccine component or 

following a prior dose 

■ Encephalopathy not 

attributable to another 

identifiable cause within 7 

days after vaccination* 

● Precaution 

■ Moderate or severe acute 

illness 

■ Progressive or unstable 

neurological disorder* 

■ Uncontrolled seizures* 

■ Progressive encephalopathy* 

■ Guillain-Barré syndrome 

within 6 weeks after a 

previous dose of tetanustoxoid containing vaccine** 

■ History of Arthus-type 

hypersensitivity reactions 

after a previous dose of 

diphtheria toxoid- or tetanus 

toxoid-containing vaccine** 

*DTaP and Tdap 

**DTaP, DT, Tdap, Td 

Immunogenicity and Vaccine Efficacy 

Since 1991, several studies conducted in Europe and Africa 

have evaluated the efficacy of DTaP vaccines administered to 

infants. These studies varied in type and number of vaccines, 

design, case definition, and laboratory method used to confirm 

the diagnosis of pertussis, so comparison among studies must 

be made with caution. Point estimates of DTaP vaccine efficacy 

ranged from 80% to 85%, with overlapping confidence intervals. 

Adolescent and adult formulation Tdap vaccines were licensed 

on the basis of noninferiority of the serologic response to the 

various components compared with each company’s pediatric 

DTaP formulation among persons who had received pediatric 

DTaP or DTP in childhood. For both vaccines, the antibody 

response to a single dose of Tdap was similar to that following 

3 doses of DTaP in infants. This type of study is known as 

“bridging.” The new vaccines are assumed to have similar clinical 

efficacy as DTaP vaccine since a similar level of antibody to the 

components was achieved. 

Studies on the persistence of antipertussis antibodies 

following a dose of Tdap show antibody levels in healthy, 

nonpregnant adults peak during the first month after 

vaccination, with antibody levels declining after 1 year. 

Because antibody levels wane substantially during the first 

year after vaccination, ACIP concluded a single dose of Tdap 

during one pregnancy would not be sufficient to provide 

protection for subsequent pregnancies. 

Contraindications and Precautions 

to Vaccination 

As with other vaccines, a history of a severe allergic reaction 

(anaphylaxis) to a vaccine component or following a prior 

dose is a contraindication to further doses. Moderate or severe 

acute illness (with or without fever) in a patient is considered a 

precaution to vaccination, although persons with minor illness 

may be vaccinated. 

Contraindications to combination vaccines that contain DTaP 

include the contraindications to the individual component 

vaccines (e.g., IPV, hepatitis B, Hib), but specific ingredients 

might differ. DTaP-HepB-IPV (Pediarix) and DTaP-IPV-HibHepB (Vaxelis) vaccines contain yeast. Presentations of some 

pertussis-containing vaccines contain latex rubber. DTaPHepB-IPV (Pediarix), DTaP-IPV/Hib (Pentacel), DTaP-IPV-Hib-HepB 

(Vaxelis), DTaP-IPV (Kinrix), and DTaP-IPV (Quadracel) contain 

neomycin and polymyxin B. DTaP-IPV-Hib-HepB (Vaxelis) 

contains streptomycin. 

Encephalopathy not attributable to another identifiable cause 

occurring within 7 days after vaccination with DTaP, DTP, or Tdap 

is a contraindication for DTaP and Tdap vaccination. 
Pertussis

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16

Pertussis-containing 

Vaccine Safety 

A progressive or unstable neurological disorder, uncontrolled 

seizures, or progressive encephalopathy is a precaution for DTaP 

and Tdap vaccination. For persons with a known or suspected 

neurologic condition, vaccination with DTaP or Tdap should 

be delayed until the condition has been evaluated, treatment 

initiated, and the condition stabilized. These conditions 

include the presence of an evolving neurologic disorder 

(e.g., uncontrolled epilepsy, infantile spasms, and progressive 

encephalopathy); a history of seizures that has not been 

evaluated; or a neurologic event that occurs between doses 

of vaccine. A family history of seizures or other neurologic 

diseases, or stable or resolved neurologic conditions (e.g., 

controlled idiopathic epilepsy, cerebral palsy, developmental 

delay), are neither contraindications nor precautions to DTaP or 

Tdap vaccination. 

Guillain-Barré syndrome within 6 weeks after a previous dose 

of tetanus toxoid-containing vaccine is a precaution for DTaP, 

Tdap, DT, and Td vaccination. 

A history of Arthus-type hypersensitivity reactions after a 

previous dose of diphtheria toxoid-containing or tetanus 

toxoid-containing vaccine is a precaution for DTaP, Tdap, DT, 

and Td vaccination; vaccination should be deferred until at 

least 10 years have elapsed since the last tetanus toxoidcontaining vaccine. 

Vaccine Safety 

DTaP vaccine may cause local reactions, such as pain, redness, 

or swelling. Local reactions have been reported in 20% to 

40% of children after each of the first 3 doses. Local reactions 

appear to be more frequent after the fourth and/or fifth doses. 

Mild systemic reactions such as drowsiness, fretfulness, and 

low-grade fever may also occur. Temperature of 101°F or higher 

is reported in 3% to 5% of DTaP recipients. These reactions are 

self-limited and can be managed with symptomatic treatment 

with acetaminophen or ibuprofen. 

Moderate or severe systemic reactions (such as fever of 105°F 

or higher, febrile seizures, persistent crying lasting 3 hours or 

longer, and hypotonic-hyporesponsive episodes) have been 

reported after administration of DTaP, but occur less frequently 

than among children who received whole-cell DTP. Rates of 

these moderate or severe systemic reactions vary by symptom 

and vaccine but generally occur in fewer than 1 in 10,000 doses. 

Exaggerated local (Arthus-type) reactions are rarely reported 

but may occur following receipt of a vaccine containing 

diphtheria or tetanus toxoids. 

The most common adverse reaction following vaccination with 

both brands of Tdap is a local reaction, such as pain (66% to 

75%), redness (25%), or swelling (21%) at the site of injection. 

DTaP 

● Pain, redness, or swelling 

■ 20%-40% 

● Temperature of 101°F 

■ 3%-5% 

● Moderate or severe systemic 

reactions 

■ Fewer than 1 in 10,000 doses 

● Arthus-type reactions are rare 

Tdap, Td 

● Pain, redness, or swelling 

■ 21%-75% 

● Temperature of 100.4°F or 

higher 

■ 1.1%-5% 
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Temperature of 100.4°F or higher was reported by 1.4% to 5% of 

Tdap recipients and 1.1% to 5% of Td recipients. Tdap recipients 

also reported a variety of nonspecific systemic events, such as 

headache, fatigue and gastrointestinal symptoms. 

The Institute of Medicine reported in 2011 that the evidence 

was inadequate to accept or reject a causal relation between 

receipt of diphtheria toxoid and tetanus toxoid-containing 

vaccine and encephalitis, encephalopathy, infantile spasms, 

seizures, ataxia, autism, acute disseminated encephalomyelitis, 

transverse myelitis, optic neuritis, onset of multiple sclerosis 

in adults, relapse of multiple sclerosis in adults, relapse of 

multiple sclerosis in children, Guillain-Barré syndrome, chronic 

inflammatory disseminated polyneuropathy, opsoclonus 

myoclonus syndrome, or Bell’s palsy. 

The most frequently reported adverse events after DTaP in the 

Vaccine Adverse Effect Reporting System (VAERS) and Vaccine 

Safety Datalink (VSD), two post-licensure surveillance systems, 

were consistent with observations from pre-licensure studies 

of these vaccines. When VAERS DTaP reports for each vaccine 

brand were compared individually with reports for all other 

inactivated vaccines in the VAERS database, no concerning 

patterns of adverse events were observed. 

Routine VAERS surveillance for and VSD studies on adverse 

events following receipt of Tdap vaccines in persons aged 10 

through 64 years have provided reassuring data consistent 

with the prelicensure clinical trial safety data and have not 

demonstrated any associations between Tdap and the following 

rare adverse events: encephalopathy-encephalitis-meningitis, 

paralytic syndromes, seizures, cranial nerve disorders, and 

Guillain-Barré syndrome. 

Vaccine Storage and Handling 

DTaP and Tdap vaccines should be maintained at refrigerator 

temperature between 2°C and 8°C (36°F and 46°F). Manufacturer 

package inserts contain additional information. For complete 

information on best practices and recommendations, please 

refer to CDC’s Vaccine Storage and Handling Toolkit, www.cdc. 

gov/vaccines/hcp/admin/storage/toolkit/storage-handling-

toolkit.pdf. 

Surveillance and Reporting of Pertussis 

For information on guidance for state and local health 

department staff who are involved in surveillance activities for 

vaccine-preventable diseases, please consult the Manual for the 

Surveillance of Vaccine-Preventable Diseases, www.cdc.gov/ 

vaccines/pubs/surv-manual/chapters.html 
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16

Acknowledgements 

The editors would like to acknowledge Jennifer Liang, 

Stacey Martin, and Cindy Weinbaum for their contributions to 

this chapter. 

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NOTES 
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