AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

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

INTRODUCTION

Section 2 of 10  

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

Background

Pertussis, commonly known as whooping cough, is a respiratory tract infection characterized by a paroxysmal cough. It was first identified in the 16th century. In 1906, Bordet isolated the most common causative organism, Bordetella pertussis. Bordetella parapertussis has also been associated with whooping cough in humans. Before the advent of vaccinations, pertussis was a major cause of morbidity and mortality among infants and children. Reported cases of pertussis decreased by more than 99% after the introduction of pertussis vaccine combined with diphtheria and tetanus toxoids in the 1940s. However, despite considerable advances in the control of infectious diseases in children through global immunization programs, pertussis remains a disease of public health concern.

Pathophysiology

Humans are the sole reservoir for B pertussis and B parapertussis. B pertussis is a gram-negative pleomorphic bacillus that spreads via aerosolized droplets from coughing of infected individuals. B pertussis attaches to and damages ciliated respiratory epithelium.

Frequency

United States

Since the early 1980s, reported pertussis incidence has increased cyclically, with peaks occurring every 3-4 years. Most cases occur between June and September. Neither acquisition of the disease nor vaccination provides complete or lifelong immunity. Protection against typical disease wanes 3-5 years after vaccination and is not measurable after 12 years.

Coughing adults, adolescents, and older children are major sources of pertussis, accounting for almost half of the reported cases between 1997 and 2000. During this period, the average annual incidence rate was 2.7 per 100,000 population.

International

In 1999, an estimated 48.5 million cases of pertussis were reported in children worldwide.

Mortality/Morbidity

Infants born prematurely and patients with underlying cardiac, pulmonary, neuromuscular, or neurologic disease are at high risk for complications of pertussis (eg, pneumonia, seizures, encephalopathy, death).

During the 1990s, the proportion of cases hospitalized was 67%, with a mean length of hospitalization of 7 days.

• The proportion of patients with pertussis who required hospitalization or developed complications was highest among infants. Of the 103 reported pertussis-related fatalities, 99% were among infants. Data from 1990-1996 showed that the most severe morbidity occurred in infants younger than 1 year. This group accounted for 82.7% of hospitalized patients, 66.28% of patients with pneumonia, 59.3% of patients who developed seizures, 71.4% of cases who had encephalopathy, and 91.2% of deaths. Pertussis has been reported as a cause of sudden infant death syndrome.
• Older children, adolescents, and adults often have mild or atypical illness.

Race

Data on race were available for 75% of patients younger than 20 years from 1997-2000. Of these patients, 88% were white, 8% were black, 2% were Asian/Pacific Islander, and 2% were American Indian/Alaska Native. In comparison, the national population estimates for persons younger than 20 years in 1998 were 79% white, 16% black, 4% Asian/ Pacific Islander, and 1% American Indian/ Alaska Native.

Sex

From 1997-2000, among pertussis cases in patients younger than 20 years, males and females were equally affected.

Age

From 1997-2000, of patients with pertussis, 29% were younger than 1 year, 12% were aged 1-4 years, 10% were aged 5-9 years, 29% were aged 10-19 years, and 20% were older than 20 years.

CLINICAL

Section 3 of 10  

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

History

Typically, the incubation period of pertussis ranges from 3-12 days. Pertussis is a 6-week disease divided into catarrhal, paroxysmal, and convalescent stages, each lasting from 1-2 weeks. The 3 stages of disease progression are as follows:

• Stage 1: The initial (catarrhal) phase is indistinguishable from common upper respiratory infections with nasal congestion, rhinorrhea, and sneezing, variably accompanied by low-grade fever, tearing, and conjunctival suffusion. Pertussis is most infectious when patients are in the catarrhal phase, but pertussis may remain communicable for 3 or more weeks after the onset of cough.
• Stage 2: Patients in the second (paroxysmal) phase present with paroxysms of intense coughing lasting up to several minutes. In older infants and toddlers, the paroxysms of coughing occasionally are followed by a loud whoop as inspired air goes through a still partially closed airway. Infants younger than 6 months do not have the characteristic whoop but may have apneic episodes and are at risk for exhaustion. Posttussive vomiting and turning red with coughing are common in affected children.
• Stage 3: Patients in the third (convalescent) stage have a chronic cough, which may last for weeks.
• Older children, adolescents, and adults may not exhibit distinct stages. Symptoms in these patients include uninterrupted coughing, feelings of suffocation or strangulation, and headaches.

Physical

• In all patients with pertussis, fever is typically absent.
• In patients with uncomplicated pertussis, physical examination contributes little to the diagnosis.
• Most patients do not have signs of lower respiratory tract disease.
• Conjunctival hemorrhages and facial petechiae are common and result from intense coughing.

Causes

• B pertussis and B parapertussis are the causative organisms for pertussis infection in humans. Bacteria spread via aerosolized droplets from coughing of infected individuals.
• Humans are the sole reservoir for the organisms.
• Young infants, especially those born prematurely, and patients with underlying cardiac, pulmonary, neuromuscular, or neurologic disease are at high risk for contracting the disease and for complications.

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Other illnesses mimicking clinical pertussis

Adenoviral respiratory infection (Children present with fever, sore throat, and conjunctivitis.)

Mycoplasmal pneumonia (Patients with mycoplasmal infections have more pronounced systemic symptoms; fever and headache may occur; rales may be appreciated on chest auscultation.)

Chlamydial pneumonia (Young infants with chlamydial infections present with staccato cough, purulent conjunctival discharge, tachypnea, rales, and wheezing.)

Respiratory syncytial virus infection (Patients present with predominantly lower respiratory tract signs [eg, wheezing, rales].)

WORKUP

Section 5 of 10  

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

Lab Studies

• Laboratory confirmation of pertussis is difficult and delayed. Therefore, clinicians need to make the diagnosis of pertussis presumptively in patients with a history of intense paroxysmal coughing with or without whooping, color changes, posttussive vomiting, incomplete or absent pertussis vaccination, and finding of lymphocytosis on laboratory examination.
• The criterion standard for diagnosis of pertussis is isolation of B pertussis in culture.
• • Obtain the culture specimen by performing deep nasopharyngeal aspiration or holding a flexible swab (Dacron or calcium alginate) in the patient's posterior nasopharynx for 15-30 seconds or until a cough is produced.
  • Promptly inoculate the sample special media (preferred are Regan-Lowe or Bordet-Gengou agar, and modified Stainer-Scholte media), and incubate for 7 days.
  • Recovery rates are highest during the catarrhal or early paroxysmal phase and low after the fourth week of illness.
  • Negative culture findings are common in patients who were previously immunized or have received antibiotics and in patients in the late phase of the illness.
• Direct fluorescent assay (DFA) of nasopharyngeal secretions is unreliable for laboratory confirmation of pertussis.
• Polymerase chain reaction (PCR) assay has the advantage of much higher sensitivity than conventional pertussis culture.
• Serologic tests are not widely available or standardized and are not diagnostic.
• Leukocytosis (15,000-50,000 10³/µL) with absolute lymphocytosis occurs during the late catarrhal and paroxysmal phases. It is a nonspecific finding but correlates with severity of the disease.

Imaging Studies

• Imaging studies typically add little to the diagnosis of pertussis but should be obtained when clinically indicated, based on examination or if the patient requires supplemental oxygen.
• Chest radiographs may show perihilar infiltrates or edema with variable degrees of atelectasis. Consolidation is indicative of secondary bacterial infection or, rarely, pertussis pneumonia. Occasionally, pneumothorax, pneumomediastinum, or air in the soft tissues may be seen.

TREATMENT

Section 6 of 10  

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

Medical Care

The mainstay of therapy in patients with active pertussis infections is supportive. The goals of therapy include limiting the number of paroxysms, observing the severity of cough, providing assistance when necessary, and maximizing nutrition, rest, and recovery.

• Hospitalization should be strongly considered for patients at risk of severe disease and complications, including infants younger than 3 months; infants aged 3-6 months, unless observed paroxysms are not severe; premature young infants; and infants or children with underlying pulmonary, cardiac, or neuromuscular disease.
• • For the hospitalized patient, in addition to standard precautions, droplet precautions are recommended for 5 days after initiation of effective therapy or until 3 weeks after the onset of paroxysms if appropriate antimicrobial therapy is not given.
  • Monitor heart rate, respiratory rate, and oxygen saturation of hospitalized patients continuously, especially in relation to coughing paroxysms. Coughing, feeding, vomiting, and weight changes should be recorded.
  • Pay attention to the young infant's hydration and nutritional status.
  • Patients who are severely ill may require treatment in an ICU.

Consultations

Consultation with subspecialists is usually not indicated; however, if diagnosis is unclear or clinical course warrants, infectious disease specialists or other subspecialists should be consulted.

Diet

• No special diet is indicated.
• A clinically age-appropriate diet should be maintained.
• Infants who cannot tolerate oral feedings may require intravenous fluids.

Activity

Activity should be guided by clinical course. In general, activity is as tolerated.

MEDICATION

Section 7 of 10  

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

Antimicrobial agents given during the catarrhal phase may ameliorate the disease. Once cough is established, antimicrobial agents may not alter the course of the illness but are still recommended to limit the spread of disease.

Pertussis-specific immune globulin is an investigational product that may be effective in decreasing paroxysms of cough but requires further evaluation.

The use of corticosteroids, albuterol, and other beta2-adrenergic agents for the treatment of pertussis is not supported by controlled, prospective data.

Drug Category: Antibiotics

The Committee on Infectious Diseases of the American Academy of Pediatrics (Red Book Committee) currently recommends promptly treating all household and other close contacts (eg, children and staff at daycare centers) with erythromycin to limit secondary transmission. This is regardless of the age or immunization status of contacts. A 14-day course of PO erythromycin is the antimicrobial therapy of choice for patients with pertussis and for close contacts. Typical dosing schedule is 40-50 mg/kg/d (not to exceed 2 g/d) in 4 divided doses. Some experts prefer the estolate preparation in young infants because of more effective absorption, which may lead to decreased dosing and less frequent dosing intervals.

In infants younger than 2 weeks, an association between orally administered erythromycin and infantile hypertrophic pyloric stenosis (IHPS) has been reported. Since pertussis can be life threatening in neonates and the efficacy of alternative therapies has not been well studied, the American Academy of Pediatrics continues to recommend the use of erythromycin for treatment of and prophylaxis for pertussis. Parents and caregivers need to be informed about the risks and signs of IHPS.

The newer macrolides (eg, azithromycin [Zithromax], clarithromycin [Biaxin]), are potential alternatives for patients who cannot tolerate erythromycin. Azithromycin is typically administered in doses of 10-12 mg/kg/d PO in 1 dose for a total of 5 days. Clarithromycin is administered at 15-20 mg/kg/d PO in 2 divided doses, not to exceed 1 g/d for 5-7 d. Trimethoprim-sulfamethoxazole (Bactrim) is another antibiotic option, with the following dosage: trimethoprim 8 mg/kg/d and sulfamethoxazole 40 mg/kg/d in 2 divided doses.

Drug Name	Azithromycin (Zithromax)
Description	Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Shown to be effective for pertussis in several small studies.
Adult Dose	500 mg PO on day 1, then 250 mg/d for the next 4 d (total 5-d course)
Pediatric Dose	10-12 mg/kg/d PO for total of 5 d
Contraindications	Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Interactions	Low risk of CYP450 3A4 inhibition; may increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	May increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients

Drug Name	Clarithromycin (Biaxin)
Description	Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Shown to be effective for pertussis in recent small studies.
Adult Dose	500 mg PO bid for 7-10 d
Pediatric Dose	15-20 mg/kg PO divided bid for 5-7 d; not to exceed 1 g/d
Contraindications	Documented hypersensitivity; coadministration of pimozide
Interactions	Inhibits CYP450 3A4 isoenzyme; toxicity increases with coadministration of fluconazole and pimozide; clarithromycin effects decrease and adverse GI tract effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, HMG-CoA–reductase inhibitors; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; give half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis

Drug Name	Trimethoprim-sulfamethoxazole (Bactrim, Septra, Cotrim)
Description	Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Alternative drug, but efficacy is unproven for pertussis.
Adult Dose	160 mg (trimethoprim component)/800 mg (sulfamethoxazole component) PO bid for 7-10 d (ie, 1 DS tab bid)
Pediatric Dose	<2 months: Contraindicated >2 months: 6-10 mg/kg/d (based on trimethoprim component) PO divided q12h for 7-10 d
Contraindications	Documented hypersensitivity; megaloblastic anemia from folate deficiency; age <2 mo
Interactions	May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Do not use in pregnancy near term due to risk of jaundice, hemolytic anemia, and kernicterus in newborn; discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBC counts frequently; discontinue if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; caution in folate deficiency (eg, elderly patients, patients with chronic alcoholism, patients receiving anticonvulsant therapy, or patients with malabsorption syndrome); hemolysis may occur in patients with G-6-PD deficiency; patients with AIDS may not tolerate or respond; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation

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 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.

Drug Name	Tdap (Adacel, Boostrix)
Description	Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine. Promotes active immunity to diphtheria, tetanus, and pertussis by inducing production of specific neutralizing antibodies and antitoxins. Indicated for active booster immunization for tetanus, diphtheria, and pertussis prevention for persons aged 10-64 y (Adacel approved for 11-64 y, Boostrix approved for 10-18 y). Preferred vaccine for adolescents scheduled for booster.
Adult Dose	One-time alternative to Td in adults when pertussis component is also indicated: 0.5 mL IM once as a single dose into deltoid muscle; at least 5 y should elapse since last dose of tetanus-, diphtheria-, and/or pertussis-containing vaccine; booster with Td recommended q10y >65 years: Not indicated
Pediatric Dose	<10 years: Not indicated 10-18 years: Administer as in adults; preferred vaccine for adolescents scheduled for booster
Contraindications	Documented hypersensitivity; encephalopathy within 7 d following pertussis-containing vaccine; progressive neurologic disorder, uncontrolled epilepsy, or progressive encephalopathy
Interactions	Patients receiving immunosuppressants, including corticosteroids or radiation therapy, may remain susceptible despite immunization because of a poor immune response
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Routine immunization of symptomatic and asymptomatic persons infected with HIV is recommended; may cause transient redness, swelling, or pain at injection site; infrequently causes fever; administer only if benefit outweighs risk to individuals with bleeding disorders (eg, hemophilia, thrombocytopenia) or those who are on anticoagulant therapy; caution if fever, shock, persistent crying, Guillain-Barré syndrome, or seizures occurred following previous DTP or DTaP vaccine (consider administering Td instead)

FOLLOW-UP

Section 8 of 10  

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

Further Inpatient Care

• Inpatient care is required for patients with intractable nausea and vomiting, failure to thrive, seizures, encephalopathy, or for patients with sustained hypoxemia during coughing paroxysms who require supplemental oxygen.
• Therapy is largely supportive but should include macrolide administration and possible use of steroids, beta2-agonists, or both.
• Antibiotics are most effective if started when the patient is in the catarrhal stage and may abort infection or at least make the patient noncommunicable. Antibiotics also may prevent or alleviate secondary bacterial infection.

Further Outpatient Care

• Most patients older than 1 year can be treated on an outpatient basis if they do not fulfill the criteria for hospital admission (see Further Inpatient Care).
• Frequent outpatient reevaluations are required; frequency of observation should be individualized based on the patient's age, disease severity, and presence of comorbid conditions.

Transfer

• Transfer of patients is usually not indicated unless inpatient therapy and monitoring is warranted and such facilities are not available at the original institution.
• Need for transfer should be evaluated on an individual basis.
• Standard monitoring and transfer protocols should be followed.

Deterrence/Prevention

• Prevention through immunization remains the best defense in the fight against pertussis.
• Since nearly all of the fatal cases of pertussis occur in infants who were too young to have been immunized, novel strategies must be explored to protect these vulnerable young infants.
• An option may be to immunize neonates with acellular pertussis vaccine. However, immunogenicity of the vaccine in newborns and possible induction of tolerance to B pertussis antigens need to be investigated.
• Evidence is overwhelming that parents and older siblings are the primary source of infection in young infants. The incidence of pertussis in preadolescents, adolescents, and adults has increased, and may be responsible for the increasing number of cases observed in young infants in some countries. In December 2005, the American Academy of Pediatrics approved recommendations from the 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 toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) products, for use in children aged 10-18 years (Boostrix; GlaxoSmithKline Biologicals, Rixensart, Belgium) and 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.

Complications

• Complications of pertussis are usually minimal, and most patients make a gradual full recovery with supportive care and antibiotics.
• Major complications include pneumonia (20%), encephalopathy, seizures (1%), failure to thrive, and death (0.3%).
• Minor complications during the illness include epistaxis, nausea and vomiting, subconjunctival hemorrhages, and ulcers of the frenulum.

Prognosis

• Prognosis for full recovery is excellent; however, patients with comorbid conditions as previously described have a higher risk of morbidity and mortality and should be evaluated on an individual basis.
• The proportion of patients with pertussis who required hospitalization or developed complications was highest among infants. Of the 103 reported pertussis-related fatalities, 90% were among infants. Data from 1990-1996 showed that the most severe morbidity occurred in infants younger than 1 year. This group accounted for 82.7% of hospitalized patients, 66.28% of patients with pneumonia, 59.3% of patients who developed seizures, 71.4% of patients who had encephalopathy, and 91.2% of deaths. Pertussis has been reported as the cause of presumed sudden infant death syndrome.
• Leukocytosis, particularly WBC counts >100,000, has been associated with fatalities from pertussis. Another study showed that WBC counts >55, 000 and pertussis complicated by pneumonia were independent predictors of fatal outcome in a multivariate model.

Patient Education

• When a diagnosis of pertussis is made, patient and parent education and individualized supportive treatment are the best options.
• All parents should receive information regarding the infectious and contagious potential of pertussis, as well as the risks derived from the vaccine.
• Prevention of pertussis involves the use of vaccine approved by the US FDA and standard infection control precautions.
• For excellent patient education resources, visit eMedicine's Children's Health Center and Public Health Center. Also, see eMedicine's patient education articles Whooping Cough and Immunization Schedule, Children.

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• Failure to diagnose pertussis
• Failure to advise patients adequately regarding the need for further observation and the risks of infection
• Potential for serious sequelae exists. Death may occur in patients with severe disease.
• Legal risks exist as a result of the potential adverse effects of vaccines.

Special Concerns

• Young infants have the highest risk for complications and death and require close observation or hospitalization.

REFERENCES

Section 10 of 10

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

• American Academy of Pediatrics. Pertussis. In: Pickering LK, ed. Red Book: 2003 Report of the Committee of Infectious Disease. 2003: 472-86.
• Centers for Disease Control and Prevention. Pertussis--United States, 1997-2000. MMWR Morb Mortal Wkly Rep. Feb 1 2002;51(4):73-6. [Medline].
• Cherry JD, Heininger U. Pertussis and other Bordetella infections. In: Feigin RD, Demmler GJ, Cherry JD, Kaplan SL, eds. Textbook of Pediatric Infection. 2004;1:1588-1608.
• Crowcroft NS, Stein C, Duclos P, Birmingham M. How best to estimate the global burden of pertussis?. Lancet Infect Dis. Jul 2003;3(7):413-8. [Medline].
• Decker MD, Edwards KM. Acellular pertussis vaccines. Pediatr Clin North Am. Apr 2000;47(2):309-35. [Medline].
• Edwards KM, Halasa N. Are pertussis fatalities in infants on the rise? What can be done to prevent them?. J Pediatr. Nov 2003;143(5):552-3. [Medline].
• Guris D, Strebel PM, Bardenheier B, et al. Changing epidemiology of pertussis in the United States: increasing reported incidence among adolescents and adults, 1990-1996. Clin Infect Dis. Jun 1999;28(6):1230-7. [Medline].
• Long S. Pertussis (Bordetella pertussis and B. parapertussis). In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 2004;17:908-912.
• Long S. Academy issues policy on adolescent pertussis vaccine. AAP News. 2006;27:1.
• Lutwick LI, Rubin LG. Childhood immunizations 2000. Introduction. Pediatr Clin North Am. Apr 2000;47(2):xi-xiv. [Medline].
• 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. Nov 2003;143(5):576-81. [Medline].
• Pierce C, Klein N, Peters M. Is leukocytosis a predictor of mortality in severe pertussis infection?. Intensive Care Med. 2000;159:898-900. [Medline].
• Tanaka M, Vitek CR, Pascual FB, et al. Trends in pertussis among infants in the United States, 1980-1999. JAMA. Dec 10 2003;290(22):2968-75. [Medline].
• Tozzi AE, Celentano LP, Ciofi degli Atti ML, Salmaso S. Diagnosis and management of pertussis. CMAJ. Feb 15 2005;172(4):509-15. [Medline].

Article Last Updated: May 23, 2006