Strange and Schafermeyer's Pediatric Emergency Medicine, Fourth Edition (Strange, Pediatric Emergency Medicine) 4th Ed.




Sharon E. Mace


• Pertussis can occur in any age group, but is most severe in infants <6 months.

• The catarrhal stage is characterized by upper respiratory tract symptoms which are followed by a paroxysmal phase characterized by staccato cough.

• Lymphocytosis is suggestive of the disease, but is not always present.

• Treatment is supportive including oxygen for hypoxia and intravenous fluids for dehydration. Macrolides limit spread of the disease and are effective if given early.

• Indications for hospital admission include infants <6 months, hypoxia, and dehydration.


Pertussis is an acute bacterial, highly contagious, respiratory infection with a significant morbidity and mortality, especially in infants.1 In the United States, prior to the advent of vaccines, pertussis was the number one cause of pediatric (age <14 years) deaths from a communicable disease, accounting for 10,000 deaths annually and was responsible for more deaths in the first year of life than measles, meningitis, scarlet fever, diphtheria, and poliomyelitis combined.2 With the widespread use of the pertussis vaccine, there was a precipitous drop (>99%) in the number of cases of pertussis, reaching a nadir in 1976, with an increase in the incidence since then with epidemic pertussis occurring every 2 to 5 years since 1989.1

It is estimated that there are about 50 to 60 million cases with 300,000 to >500,000 deaths annually attributable to pertussis.1,3,4 There is a high incidence of pertussis in developing countries and nations with low vaccination rates. In the United States and Europe, in spite of widespread vaccination, the incidence of pertussis has been increasing.26 Considering just adolescents and adults, the number of pertussis cases per year in the United States is calculated to be around 600,000.1

In the United States, substantial epidemics occur every few years (e.g., in 2005, 2010, and 2012), with 2012 possibly the largest outbreak in 50 to 60 years.7,8 The resurgence of this vaccine-preventable disease has been attributed to several factors: (1) increased awareness of the disease, (2) availability of better laboratory tests for detection of Bordetella pertussis, (3) genetically modified changes in B. pertussis, (4) vaccine failures secondary to decreased potency of the vaccines, and (5) unimmunized individuals for religious or other reasons.

After immunization, there is a decline in antibody titers over time.5,79,11 Immunity begins to drop off during the third to fifth year after vaccination and is essentially nonexistent after 12 years.1,1214 It is important to note that neither infection with pertussis (natural disease) nor vaccination provides lifelong or complete immunity against future reinfection or disease due to B. pertussis. The whole-cell vaccine, DTP vaccine, is more potent than the acellular vaccines, DTaP and Tdap vaccines, but has more side effects so the acellular vaccines are currently used (exclusively used since 1997) in the United States for immunization.10


Pertussis is transmitted in aerosolized droplets during coughing and is highly contagious, with attack rates in close contacts as high as 90% to 100% and for school contacts about 50%.4,5,14 Patients are most infectious during the catarrhal and early paroxysmal phases of the disease. Coughing adolescents and adults are the reservoir for B. pertussis and generally transmit the infection to infants and young children. In one study, household members were responsible for 76% to 83% of transmission of B. pertussis to infants.15

B. pertussis has an affinity for human respiratory tract epithelium and does not spread to the bloodstream which likely accounts for infected patients being afebrile, nontoxic appearing, and with no bacteremia. It produces numerous substances or toxins that increase its virulence, including the pertussis toxin.1


The clinical definition for pertussis is an acute cough illness ≥14 days, plus one or more of the following: paroxysms of coughing, inspiratory whoop, or post-tussive emesis.1 Pertussis or “whooping cough” is characterized by severe episodes of coughing followed by a forceful inspiration against a partially closed glottis, which causes the classic whooping sound.

Pertussis has a 3- to 12-day incubation period, which lasts 6 to 10 weeks, and is characterized by three stages: catarrhal, paroxysmal, and convalescent. The catarrhal phase, which lasts 1 to 2 weeks, consists of nonspecific upper respiratory infection (URI) symptoms. If fever is present, it is low grade (Table 37-1).

TABLE 37-1

Three Stages of the Disease


The next stage is the paroxysmal phase, characterized by paroxysms of coughing with an increased frequency at night and lasts from 1 to 6 weeks. There will be 10 to 15 consecutive rapid- fire coughs, the patient looks anxious, their face turns red or purple, their eyes bulge, their tongue protrudes, and they may have an inspiratory whoop and post-tussive emesis. During the convalescent phase, the coughing episodes decrease in severity, except in infants.


Many patients lack the classic signs and symptoms and/or have an atypical presentation. The classic form of pertussis occurs most frequently as a primary infection in unimmunized children, whereas atypical presentations are the rule in infants and adults.

Young infants, especially those ≤3 months of age, usually do not have the classic three-stage presentation. The catarrhal phase may be unrecognized or shortened to a few days. The cough (expiratory grunt) and the whoop (forceful inspiratory gasp) may not be a prominent finding.

Infants may have choking, gasping, and apnea, which may be triggered by minimal stimulation, such as from a sound or light, from sucking, stretching, or even suctioning. Apnea may be the only manifestation of the disease. The coughing may worsen during the convalescent phase instead of gradually getting better. Infants may have a prolonged convalescent stage with episodic paroxysmal spells triggered by other (nonpertussis) illnesses. Another presentation of pertussis in infants younger than 6 months is “silent” paroxysms. The infant appears to be coughing or not breathing with no audible sounds and may even become unresponsive.

Adolescents and adults generally present with prolonged cough and do not have the characteristic whoop or the three distinct stages; though they can have subclinical, mild symptomatic disease, or even classic pertussis. Age, previous immunization or infection, antibiotic treatment, and the presence of passively acquired antibodies affects the clinical presentation. One-fourth of college students (26%) with a cough for 6 or more days had culture proven B. pertussis and none were diagnosed clinically.16 Similar results have been noted in adults, with a 20% to 21% incidence of B. pertussis by laboratory testing.17,18The lack of findings on physical examination, the absence of a fever or a low-grade fever, and lack of sputum tends to make health care practitioners overlook the diagnosis of pertussis. Occasionally, adults and adolescents with pertussis will present with syncope from the severe coughing spells.

Physical examination in patients with pertussis is usually unremarkable with a normal lung examination, unless a complicating pneumonia is present. However, severe coughing may lead to conjunctival hemorrhages and petechiae, a torn frenulum in infants, and subcutaneous emphysema.1


Consider pertussis in any individual with the main complaint of cough, particularly if they lack the following signs or symptoms: myalgias, malaise, exanthem, enanthem, fever, tachypnea, and have a “normal” lung examination without wheezing, rales, or rhonchi; and a “normal” chest roentgenogram.

Pertussis should be considered in infants with any of the following: gasping, gagging, cyanosis, apnea, or an apparent life-threatening event (ALTE) and has been linked to sudden infant death.1 It should be in the differential diagnosis of an older child with a cough that is worsening at 7 to 10 days and any individual with a prolonged cough.1 About half of the adolescents with pertussis will cough for 10 weeks or longer.

Indeed, pertussis means “violent cough” and has been dubbed the cough of 100 days.4

Several other respiratory pathogens can cause a prolonged, repetitive cough including other Bordetella species (e.g., B. parapertussisB. holmesii), Mycoplasma pneumoniaeClamydophila pneumoniae, adenovirus, bocavirus, and others.1,3 Coughing episodes are also associated with respiratory diseases: asthma and cystic fibrosis; pulmonary infections: pneumonia, bronchiolitis, tuberculosis; and fungal infections: coccidioides, histoplasmosis. Cough may also be related to airway foreign body, sinusitis, and gastroesophageal reflux.

Concurrent infection with respiratory syncytial virus (RSV) and adenovirus has been noted frequently. A recent study noted that one-third of hospitalized infants with pertussis (documented by positive B. pertussis cultures) also had a concurrent RSV infection.19


B. pertussis belongs to the Bordetella genus of bacteria, which consists of small, gram negative, pleomorphic, aerobic coccobacilli. B. pertussis affects only humans and has no known animal or environmental reservoir.3 B. parpertussis causes 2% to 20% of pertussis cases, is clinically similar to B. pertussis infection, but is usually less severe. B. holmesii has been associated with respiratory infections in humans and other mammals, but has not been well studied.3 B. bronchiseptica has been reported to cause a severe respiratory illness in immunocompromised patients, for example, AIDS patients; and is the organism responsible for “kennel cough” in animals.

Recently, B. holmesii was found in 20.3% of samples and nearly one-third of the samples in two outbreaks of pertussis (in France and United States, respectively).20,21 Coinfections with both B. pertussis and B. holmesii were also reported in the outbreak in the United States.21 Whether this is a new trend remains to be seen. It is also possible that the pertussis vaccine may not fully protect against these other Bordetella species, which could be another reason for “vaccine failure.”21

The gold standard for the laboratory confirmation of pertussis has been bacterial culture, which is specific (95%) with a low sensitivity (15%–45%), but allows for antibiotic susceptibility testing and DNA fingerprinting.14,22 B. pertussis is a very fastidious organism that requires special enhanced culture media (Bordet-Gengou or Regan-Lowe), which is not always readily available, generally takes 3 to 7 days to grow, is more difficult to grow if the patient has received antibiotics or is in the later paroxysmal stage. If nasopharyngeal swabs are used, they should be calcium alginate, dacron or rayon, not cotton swabs since cotton will inhibit the growth of B. pertussis.2,5

Direct fluorescent antibody testing (DFA) of nasopharyngeal secretions using specific antibody for B. pertussis and B. parapertussis can yield results within several hours, but has low sensitivity and specificity, and may have cross reactivity with other organisms.2 Thus, it has been replaced by PCR testing and is no longer recommended.10 PCR testing has a higher sensitivity than culture, a high specificity (>95%), and rapid results (usually <48 hours). However, false positives can occur secondary to contamination, the methods are not universally standardized or validated, and laboratories require adequately trained personnel with appropriate quality control measures.2,5 Some experts recommend doing both a culture and PCR during the infectious period, which is about 4 weeks from symptom onset (e.g., start of catarrhal stage) or 3 weeks from onset of cough (e.g., beginning of paroxysmal phase).14,22


In infants and young children in the catarrhal stage, leukocytosis from 15,000 to 40,000 cells/mm3 is generally present, but may reach 100,000 cells/mm3. This is secondary to an absolute lymphocytosis of normal small, size lymphocytes. This is unlike the large atypical lymphocytes found with viral illnesses such as mononucleosis, which may serve as a clue to the disease. The lymphocytosis suggestive of pertussis may be only mildly elevated in young infants and may be absent in adolescents and adults.10,23

Polymorphonuclear leukocytosis implies a secondary bacterial infection or another infection/disease. Extreme leukocytosis and/or thrombocytosis are associated with increased disease severity and death. The pertussis toxin causes leukocyte dysfunction and histamine sensitivity, in addition to stimulating insulin secretion, which infrequently causes hypoglycemia. It is important to check a blood sugar in patients with pertussis.1

The chest radiograph is frequently normal, although mild abnormalities such as increased peribronchial cuffing or patchy atelectasis may be present. Parenchymal consolidation, especially if the patient is febrile, generally indicates a secondary bacterial infection. With severe paroxysmal coughing, subcutaneous emphysema, pneumomediastinum or pneumothorax may be present.


The overall complication rate in a large, multicenter European study was 6%, but was 24% in infants younger than 6 months.24 Apnea, pneumonia, respiratory failure, and dehydration/weight loss from vomiting and trouble feeding are the most common complications. Seizures and death are infrequent complications of pertussis.

Apnea is a complication occurring almost entirely in infants, particularly those younger than 6 months. One Canadian study found that nearly one-third (31%) of children younger than 2 years had apnea,25whereas another study found a 16% incidence of apnea in infants younger than 6 months.24

Pneumonia may occur primarily or secondarily. One German study of pediatric and adult patients with pertussis noted a 5.8% rate of complications, with pneumonia being the most frequent complication at 29% followed by apnea at 12.6%. In a Canadian study of children <2 years of age, the incidence of apnea was 27.1%, and pneumonia in 9.4%.25 The Centers for Disease Control reported similar results in children younger than 6 months, who had a 12% to 13% incidence of pneumonia documented by chest radiograph.26,27

Vomiting is common with a cited incidence of 50% to 53% in several studies.24,25 Neurologic complications of pertussis are rare with new-onset seizures reported in 1% to 2% of children (age <2 years old) and encephalopathy in <1% (probably due to hypoxia).25

The mortality from pertussis is <1% with the overwhelming majority of deaths occurring in patients <6 months of age, accounting for 86% of the deaths in one study.26 Similarly, hospitalization rates are greatest for infants younger than 6 months (up to 80%), followed by infants aged 6 to 11 months (30%), and lowest for adolescents (10%).27

Factors associated with an increased risk of death (other than young age) are intubation for pneumonia, leukocytosis, and pneumonia at initial presentation.28 Pertussis is considered an infrequent cause of sudden infant death due to fatal apnea in infants with pertusis. It has been suggested that SIDS infants be evaluated for pertussis, especially if there is a history of cough in the infant and/or family members.

An association between hypertrophic pyloric stenosis (HPS) and the use of erythromycin or azithromycin for the treatment of pertussis has been reported.29 This led to the recommendation that HPS be considered in any young infant who develops vomiting within 1 month of macrolide therapy given as a neonate.


The management of pertussis focuses on supportive care ranging from avoidance of triggers for paroxysmal coughing, such as cold ambient temperatures, strenuous activity, and even suctioning, to hospitalization for careful monitoring.10

Reasons for admission to the hospital include infants less than 6 months of age; respiratory complications such as apnea, cyanosis, pneumonia, or respiratory distress; or neurologic complications including seizures or encephalopathy; or dehydration/weight loss from the vomiting and inability to feed. Place the patient in respiratory and secretion isolation. Monitor respiratory rate, heart rate, and oxygen saturation. Some patients may need intravenous hydration and/or nasogastric feedings.

Antimicrobial therapy is recommended in any patient considered to have clinical pertussis or a laboratory-verified diagnosis of pertussis, even if asymptomatic. Antibiotic therapy may shorten the duration and severity of symptoms if given early. The variable results of treatment are likely due to the time when treatment was started and the stage of the illness. Antibiotic therapy also eliminates nasopharyngeal carriage and is very important in infants younger than 6 months. If untreated, they have a greater risk of complications.30

The antibiotics of choice are the macrolide class. All three macrolides, erythromycin, clarithromycin, and azithromycin, are effective, although erythromycin may not be well tolerated due to the gastrointestinal side effects.10However, azithromycin is the drug of choice.10 Trimethoprim-sulfamethoxazole (TMP-SMX) is an alternative antibiotic in patients in whom a macrolide is contraindicated or not tolerated due to side effects.10 TMP-SMX is contraindicated in late trimester of pregnancy because of the potential for bilirubin displacement and risk of kernicterus in the fetus and infant. Other antibiotics are not recommended because of inconsistent bactericidal activity against B. pertussis (as with the β-lactam antibiotics, for example, cephalosporins, ampicillin, amoxicillin), failure to eradicate nasopharyngeal carriage (e.g., ampicillin, amoxicillin), or possible adverse effects in children (doxycycline, fluoroquinolones).

One should treat infants older than 1 month and younger than 6 months with a macrolide antibiotic, according to both the Red Book (American Academy of Pediatric Committee on Infectious Diseases) and the CDC; even though azithromycin and clarithromycin are not approved by the United States Food and Drug Administration for use in infants younger than 6 months.10 The newer macrolides appear to be better tolerated and have a more convenient dosing schedule than erythromycin, although erythromycin is less expensive. For neonates (age <1 month), both the Red Book and the CDC recommend azithromycin (fewer side effects and has not been associated with idiopathic hypertrophic pyloric stenosis) (see Table 37-2 for dosages).10,31

TABLE 37-2

Oral Dosages Recommended




Antimicrobial prophylaxis is given at the same dosage as for treatment. Prophylaxis can prevent the development of symptoms when given to asymptomatic contacts within 21 days of the onset of cough in the index case, although efficacy after 21 days is not established.

Antimicrobial prophylaxis is recommended for all close contacts (irrespective of immunization status), although widespread prophylaxis for an entire classroom/school is not recommended.10 Close contacts include household members and childcare workers. In the health care setting, close contacts are individuals who have had direct contact with secretions (nasal, oral, or respiratory) from a symptomatic patient or who had a face-to-face exposure within 3 ft of a symptomatic patient, or shared the same confined space in close proximity with a symptomatic patient for ≥1 hour. Nosocomial outbreaks are aborted by antimicrobial prophylaxis of exposed health care workers (HCWs) and patients.

Antibiotic prophylaxis is also recommended for exposed individuals at high risk for severe or complicated pertussis. High-risk patients include young age (<1 year especially <4 months), immunodeficient patients, and/or those with significant comorbidity (e.g., chronic lung disease, respiratory insufficiency). Women in the third trimester of pregnancy should also be given postexposure prophylaxis because of the high risk to young infants.


Vaccination is very effective, conferring 95% protection against severe disease and 64% protection against mild disease. There are two types of pertussis vaccine: killed whole-cell vaccine and acellular vaccine. The acellular vaccine has fewer reactions, is more expensive, and is the vaccine used in the United States. The whole-cell vaccine has more side effects but is widely used in the developing world. The Red Book and the CDC recommend routine vaccination of children and adolescents with five doses of diphtheria, tetanus toxoid, and acellular pertussis (DTaP) at 2, 4, 6, 15, and 18 months and 4 to 6 years of age.10

With the resurgence of pertussis in recent years, a booster vaccination (Tdap) in adolescents and adults is recommended, either adacel (for ages 11–64 years) or boostrix (for age ≥10 years). Recently, according to the Advisory Committee on Immunization Practices (ACIP), adacel can be given to patients ≥65 years old. The booster immunization (Tdap) for previously immunized individuals differs from DTaP used for primary immunization in that it contains lower quantities of the diphtheria and pertussis toxoids than the equivalent pediatric DTaP (daptacel or infantrix).


Isolation using standard precautions and droplet precautions (mask within 3 ft) are recommended for hospitalized pertussis patients until 5 days after effective therapy has ended or 3 weeks after symptom onset in untreated patients. Patients with pertussis should not return to work in health care facilities, day care, or schools until after antibiotic therapy for 5 days, and should stay away from infants/young children, especially if they have not been immunized.


Pertussis (whooping cough) is an acute, highly communicable respiratory disease caused by B. pertussis. It is the only vaccine-preventable disease which is on the increase in the United States. In young children, especially infants, pertussis can be a life-threatening illness. There are several new recommendations for pertussis vaccination in adolescents, adults, and for health care personnel. Pertussis should be in the differential diagnosis in a patient of any age with a cough, especially if the cough is severe or prolonged.


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20. Njamkepo E, Bonacorsi S, Debruyne M, et al. Significant finding of Bordatella holmesii DNA in nasopharyngeal samples from French patients with suspected pertussis. J Clin Microbiol. 2012;49:4347.

21. Kuehn BM. Report highlights new cause of pertussis, tick-borne illness and better food safety. JAMA. 2012;307:1785.

22. Crowcroft NS, Pebody RG. Recent developments in pertussis. Lancet. 2006;367:1926.

23. Guinto-Ocampo H, Bennett JE, Attia MW. Predicting pertussis in infants. Pediatr Emerg Care. 2008;24:16.

24. Heininger U, Klich K, Stehr K, et al. Clinical findings in Bordatella pertussis infections: results of a prospective, multicenter surveillance study. Pediatrics. 1997;100:e10.

25. 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.

26. Guris D, Strebel PM, Bardenheier B, et al. Changing epidemiology of pertussis in the United States: increased incidence among adolescents and adults, 1990–1996. Clin Infect Dis. 1999;28:1230.

27. Raguckus SE, Vanden Bussche HL, Jacobs C, et al. Pertussis resurgence: diagnosis, treatment, prevention, and beyond. Pharmacotherapy. 2007;27:41.

28. Mikelova LK, Halperin SA, Scheifele D, et al. Predictors of death in infants hospitalized with pertussis: a case controlled study of 16 pertussis deaths in Canada. J Pediatr. 2003;143:576.

29. Mahon BE, Rosenman MB, Kleinman MB. Maternal and infant use of pyloric erythromycin and other macrolide antibiotics as risk factors for infantile hypertrophic stenosis. J Pediatr. 2001;139:380.

30. (includes link to Pertussis Epidemic—Washington, 2012. MMWR Morb Mortal Wkly Rep. 2012;61(28):517). Accessed January 22, 2013.

31. The Medical Letter 54(1399):73, September 187, Pertussis—United States, 2001–2003.