AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

In the prevaccination era, pertussis (ie, whooping cough) was a leading cause of infant death. The number of cases reported had decreased by more than 99% from the 1930s to the 1980s. However, because of many local outbreaks, the number cases reported in the United States increased by more than 2300% between 1976 and 2005, when the recent peak of 25,616 cases were reported. The disease is still a significant cause of morbidity and mortality in infants younger than 2 years. Pertussis should be included in the differential diagnosis of protracted cough with cyanosis or vomiting, persistent rhinorrhea, and marked lymphocytosis.

Pathophysiology

Bordetella pertussis is an aerobic, nonmotile, gram-negative coccobacillus that attaches to and multiplies on the respiratory epithelium, starting in the nasopharynx and ending primarily in the bronchi and bronchioles. Transmission is only human to human by means of exposure to aerosol droplets. The disease is highly contagious. Approximately 80-90% of susceptible individuals who are exposed develop the disease. Most cases occur in the late summer and early fall.

A mucopurulosanguineous exudate forms in the respiratory tract. This exudate compromises the small airways (especially those of infants) and predisposes the affected individual to atelectasis, cough, cyanosis, and pneumonia. The lung parenchyma and bloodstream are not invaded; therefore, blood culture results are negative.

Frequency

United States

The rate of pertussis peaked in the 1930s, with 265,269 cases and 7518 deaths reported in the United States. This rate decreased to a low in 1976, when 1010 cases and 4 deaths occurred. The rate recently peaked to 25,616 cases (8.7 cases per 100,000 people per year) reported to the Centers for Disease Control and Prevention (CDC) in 2005 and 15,632 (5.2 per 100,000) reported in 2006. The CDC estimates that 5-10% of all cases of pertussis are recognized and reported. Pertussis remains the most commonly reported vaccine-preventable disease in the United States in children younger than 5 years.

In reported studies, 12-32% of adults with prolonged (1-4 wk) cough have pertussis.

International

In England, the percentage of people vaccinated over the last 4 decades decreased to less than 30%. This decline has resulted in thousands of cases reported recently, a rate that approaches the incidence in the prevaccination era. Similar epidemic outbreaks have recently occurred in Sweden, Canada, and Germany. Nearly 300,000 deaths from pertussis in Africa are thought to have occurred over the last decade.

Mortality/Morbidity

The mortality rate had been greater than 50%. Now, the mortality rate for hospitalized patients in the United States and in Europe is about 1 per 500 cases (<0.2% of those reported). The overall infant mortality rate is 2.4 per 1 million live births. The CDC reported 39 deaths from pertussis in 2005; 32 (82%) occurred in infants younger than 3 months. The World Health Organization (WHO) estimates that 294,000 children died from pertussis worldwide in 2002.

• About 90-95% of patients die from secondary pneumonia, dehydration, hypoxia, encephalopathy, or cerebral hemorrhage. Cerebral hemorrhage occurs secondary to paroxysmal coughing, which elevates the intracranial pressure (ICP).
• Today, about 10-25% of children younger than 4 years and 2-4% of all persons with pertussis secondarily develop bacterial pneumonia. Approximately 1-2% of infants and 0.3-0.6% of adults develop seizures, which are believed to be a result of hypoxia or cerebral hemorrhage from the prolonged coughing spells. About 0.1% develop encephalopathy.
• In the prevaccination era, pertussis caused more than 270,000 cases and nearly 10,000 deaths annually. This rate reached a low of 4 reported deaths in the United States in 1982 and has recently risen to an average of about 25 deaths annually, with 39 being reported in 2005.

Sex

Pertussis is more common in girls than in boys.

Age

• Pertussis occurs predominantly in those aged 3 months to 5 years, with more than 70% of cases reported in children younger than 5 years.
• Because of the lack of maternal immunity transfer, 10-15 % of all cases occur in infants younger than 6 months, yet more than 90% of all deaths occur in this same age group.  However, the growing majority of cases are now in those aged 10 years and older, which has led to increased booster recommendations.
• The natural disease does not provide lifelong immunity as earlier thought. Three injections of the cellular or acellular vaccine provide up to 12 years of protection. These vaccinations help account for the more than 10-fold increase reported in those older than 18 years.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

• Pertussis typically consists of 3 stages: incubation, catarrhal, and paroxysmal.
• The asymptomatic incubation period lasts 7-10 days.
• The catarrhal stage follows and lasts about 2-7 days. Findings include the following:
• • Minimal or no fever
  • Rhinorrhea
  • Anorexia
  • Mild but increasing cough
• The paroxysmal stage follows, lasting about 1-8 weeks.
• • It is characterized by paroxysms of coughing, which are provoked by feeding (in infants) and exertion.
  • These paroxysms are less spontaneous than those observed in typical respiratory infections.
  • The inspiratory gasp or whoop eventually develops, especially in those aged 6 months to 5 years.
• Infants younger than 6 months often have vomiting in association with the cough, which leads to dehydration.
• • Hypoxia tends to be more severe than what the child's clinical appearance suggests.
  • A substantial number of patients present with cyanosis and apneic spells.
• Vaccinated adults usually develop only prolonged bronchitis without a whoop, whereas unvaccinated adults are most likely to have whooping and posttussive emesis.
• About 12-32% of adults with persistent cough (>2 wk) have pertussis. On average, they wait a median of 3 weeks before seeking treatment.

Physical

• The classic inspiratory gasp or whoop primarily develops in those aged 6 months to 5 years. It is usually absent in those younger than 6 months and in most older vaccinated children and adults; however, it can often be observed in unvaccinated adults, as can posttussive emesis.
• Hypoxia should be considered and assessed.
• Dehydration is common on presentation.
• Mild fever is common. Fever with a temperature of over 39°C is rare.

Causes

• The main causative organism is B pertussis.
• Bordetella parapertussis and Bordetella bronchiseptica are less common than B pertussis and produce a clinical illness that is similar but milder to pertussis due to B pertussis.
• Risk factors include the following:
• • Nonvaccination in children
  • Contact with an infected person
  • Epidemic exposure
  • Pregnancy

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Other Problems to be Considered

Common cold
Adenoviral syndromes
Influenza
Cystic fibrosis
Interstitial pneumonitis

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Lab Studies

• Blood work
• • Lymphocytosis is often profound (>70% of the total WBC count), especially in children.
  • The WBC count often increases to 20-40,000 or even 100,000 cells/mm².
  • In adults, especially those that had been vaccinated, lymphocytosis is rare.
• Cultures
• • A definitive culture diagnosis is not always possible.
  • Results of blood culture are uniformly negative because B pertussis grows solely in the respiratory epithelium.
  • An immediately plated, deep, culture of a nasopharyngeal swab sample grown in Regan-Lowe charcoal agar or fresh Bordet-Gengou is considered the criterion standard for those who present within the first 3 weeks of their cough. The results are positive in <50% (perhaps 15-40%) of cases, and results become available too late (about 1 week) to be clinically useful. The CDC recommends this test to characterize the illness.
• Direct fluorescent antibody (DFA) studies
• • DFA studies are performed by using a nasopharyngeal sample.
  • Although the results can be available within minutes, its use is not recommended because of both low sensitivity and low specificity.
  • Results are positive in 40-80% of patients and are now used to confirm most cases.
  • Specimens should be obtained within the first 3 weeks of the disease (ie, in incubation, catarrhal, or early paroxysmal stages) or the sensitivity and specificity decrease.
• Polymerase chain reaction (PCR) testing to detect DNA
• • PCR testing may reveal <10 organisms per swab sample.
  • Its sensitivity may be greater than that of culturing.
  • False-positive results have been a problem, with some reports of more than 50%. Although this or a positive culture is the case definition for reporting pertussis to the CDC or WHO, some are now recommending ELISA confirmation before declaring an epidemic.   
• Enzyme-linked immunosorbent assay (ELISA) is also useful. Many now consider serologic testing with ELISA to be the criterion standard.

Imaging Studies

• Chest radiography may show focal atelectasis and/or peribronchial cuffing.
• The CDC recommends both culture and PCR tests if a patient has a cough lasting longer than 3 weeks.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Emergency Department Care

• General supportive measures (eg, oxygenation, breathing treatments, mechanical ventilation) should be administered as needed.
• Infants should be carefully observed for apnea, cyanosis, or hypoxia.
• Patients should be isolated from susceptible individuals (especially infants) for 4 weeks, especially until 5-7 days of antibiotic therapy is completed. When patients present with paroxysmal cough, the clinical course is not shortened, but transmission is considerably decreased after 5 days of therapy.
• Factors that should prompt a consideration of admitting the patient are the following:
• • Age younger than 1 year
  • Pneumonia
  • Apneic or cyanotic spells or hypoxia
  • Moderate-to-severe dehydration
• The effectiveness of prophylaxis for exposed susceptible persons has not been determined; however, it is recommended for household and close contacts of the patient. Regimens include the following:
• • Erythromycin 50 mg/kg/d divided 4 times a day (qid) for 14 days
  • Alternative: Clarithromycin 7.5 mg/kg 2 times a day (bid) for 14 days (The effectiveness of clarithromycin has not been proven but is inferred.)

Consultations

Pertussis is a reportable infectious disease in the United States.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.

Erythromycin is the antibiotic treatment of pertussis. If the patient is allergic to erythromycin, use trimethoprim sulfamethoxazole (TMP-SMZ).

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug Category: Vaccines

Active immunization increases resistance to infection. Vaccines consist of microorganisms or cellular components that act as antigens. Administration of the vaccine stimulates the production of antibodies with specific protective properties.

The need for prevention of pertussis through immunization cannot be overemphasized. All children younger than 7 years should receive the pertussis vaccine. In the United States, acellular pertussis vaccine is recommended and usually is combined with diphtheria and tetanus toxoids (DTaP). When possible, the same DTaP vaccine product should be used for the first 3 doses of the pertussis immunization series. Reduced-volume dosing is not recommended. Measurable antibody wanes after 3-5 years and is not measurable 12 years after vaccination has been completed. Vaccine may not prevent the illness entirely, but it has been shown to lessen disease severity and duration.

Adolescents and adults have been identified as the source of pertussis transmission to infants, from household contact studies and outbreak investigations. Infectious disease experts are currently investigating the most efficacious and cost-effective means of preventing disease transmission to infants, who are at highest risk of severe disease. Options include vaccination of adolescents and adults in close contact with infants, maternal vaccination to provide passive antibody protection to the infant, and vaccinating infants with acellular pertussis vaccine at birth.

In December 2005, the American Academy of Pediatrics approved recommendations from the Committee on Infectious Diseases (COID) for universal vaccination of adolescents at the 11- or 12-year visit to boost protection against pertussis. The Food and Drug Administration (FDA) has licensed 2 tetanus toxoids (Td), reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) products, for use in children aged 10-18 years (Boostrix; GlaxoSmithKline Biologicals, Rixensart, Belgium) and in those aged 11-64 years (Adacel; Sanofi Pasteur, Toronto, Canada). Tdap will replace Td in the childhood immunization schedule. The effectiveness of this strategy has yet to be demonstrated.

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Deterrence/Prevention

• Whole-cell vaccination
• • The vaccine, used from the 1940s until the mid-1990s in the United States and from the 1940s until the 1980s in Europe, consisted of a whole cell with endotoxin given in 4 doses. About 80% of recipients acquired effective protection with this regimen. Two doses provided some immunity, whereas 1 dose provided little protection.
  • About 50% of patients have a local reaction, 1 in 1750 have a seizure without fever, 10.5 per million have encephalitis, and permanent brain damage is rare. Concern about CNS adverse effects is a major reason why many individuals choose not to be vaccinated.
• Acellular vaccination
• • Vaccination is now recommended with DTaP at the ages of 2, 4, 6, and 15-18 months, and 4-6 years of age. A booster with Tdap (DTaP is not recommended for children aged 7 years or older) is recommended instead of one Td booster from age 19 and up. Tdap is not recommended in pregnancy.
  • After immunization, fever is reported in 3-5% of patients, persistent crying in 12 per 100,000, febrile seizures in 5 per 100,000, afebrile seizure in 2 per 100,000, and hyporesponsive episodes in 5 per 100,000. Severe neurologic sequelae have not been reported. This is about the same as Td alone.

Complications

• Pneumonia
• Hypoxic encephalopathy
• Otitis media
• Tuberculosis activation
• Epistaxis, hemoptysis
• Hernia
• Reinduction of paroxysmal coughing with upper respiratory infections
• Seizures
• Cerebral hemorrhage
• Coma and death

Prognosis

• With treatment, complete recovery is expected.

Patient Education

• For excellent patient education resources, visit eMedicine's Common Childhood Illnesses Center and Children's Health Center. Also, see eMedicine's patient education articles Whooping Cough and Immunization Schedule, Children.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

• Aoyama T, Sunakawa K, Iwata S, et al. Efficacy of short-term treatment of pertussis with clarithromycin and azithromycin. J Pediatr. Nov 1996;129(5):761-4. [Medline].
• Bass JW, Stephenson SR. The return of pertussis. Pediatr Infect Dis J. Feb 1987;6(2):141-4. [Medline].
• Centers for Disease Control and Prevention. Vaccine preventable deaths and the Global Immunization Vision and Strategy, 2006-2015. MMWR Morb Mortal Wkly Rep. May 12 2006;55(18):511-5. [Medline]. [Full Text].
• Centers for Disease Control and Prevention. Outbreaks of respiratory illness mistakenly attributed to pertussis--New Hampshire, Massachusetts, and Tennessee, 2004-2006. MMWR Morb Mortal Wkly Rep. Aug 24 2007;56(33):837-42. [Medline]. [Full Text].
• Centers for Disease Control and Prevention. Recommended Adult Immunization Schedule-United States, October 2007-September 2008. MMWR Morb Mortal Wkly Rep. Oct 19 2007;56(41):Q1-Q4. [Full Text].
• Centers for Disease Control and Prevention. Recommended Immunization Schedules for Persons Aged 1--18 Years ---United States, 2008. MMWR. 2008;56(51&52):Q1-Q4.
• Geier DA, Geier MR. An evaluation of serious neurological disorders following immunization: a comparison of whole-cell pertussis and acellular pertussis vaccines. Brain Dev. Aug 2004;26(5):296-300. [Medline].
• He Q, Viljanen MK, Arvilommi H, et al. Whooping cough caused by Bordetella pertussis and Bordetella parapertussis in an immunized population. JAMA. Aug 19 1998;280(7):635-7. [Medline].
• Nennig ME, Shinefield HR, Edwards KM, et al. Prevalence and incidence of adult pertussis in an urban population. JAMA. Jun 5 1996;275(21):1672-4. [Medline].
• Roush SW, Murphy TV,. Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States. JAMA. Nov 14 2007;298(18):2155-63. [Medline].
• Tindberg Y, Blennow M, Granstrom M. A ten year follow-up after immunization with a two component acellular pertussis vaccine. Pediatr Infect Dis J. Apr 1999;18(4):361-5. [Medline].
• Ward JI, Cherry JD, Chang SJ, Partridge S, Lee H, Treanor J. Efficacy of an acellular pertussis vaccine among adolescents and adults. N Engl J Med. Oct 13 2005;353(15):1555-63. [Medline].
• Wright SW, Edwards KM, Decker MD, Lamberth MM. Pertussis seroprevalence in emergency department staff. Ann Emerg Med. Sep 1994;24(3):413-7. [Medline].
• Wright SW, Edwards KM, Decker MD, Zeldin MH. Pertussis infection in adults with persistent cough. JAMA. Apr 5 1995;273(13):1044-6. [Medline].

Article Last Updated: Jan 16, 2008