Beverly L. Connelly
The World Health Organization estimated in 2002 that nearly 300,000 children died from pertussis.1 In the United States, in spite of widespread vaccination there has been a steady rise in the number of pertussis cases reported to the Centers for Disease Control and Prevention (CDC) over the past the last decade, punctuated by several statewide outbreaks in 2004 and 2005.2-5
Pertussis occurs year-round in the United States, although the disease peaks in the summer and fall in most locations. Humans are the only reservoir for Bordetella pertussis, and transmission from person to person occurs via respiratory droplets. Attack rates following household exposure have been reported as high as 90% for unimmunized children.6-8 Attack rates in adult household contacts are at least 30%.6Communicability is highest early in the disease, but may persist for weeks in some individuals.8 Unrecognized disease serves as a reservoir for spread of infection.
Infants younger than 6 months of age have the highest burden of disease.9 Hospitalizations and mortality from pertussis are highest in infants under 3 months of age.10 Passively acquired transplacental antibodies afford little protection, and vaccine-induced immunity requires multiple immunizations. Based on CDC surveillance data from 2000 to 2003, 86% of hospitalizations for pertussis occur in infants less than 3 months of age.10 Apnea and respiratory distress were the most frequent complications, followed by pneumonias. Mortality is greatest in infants less than 3 months of age. The frequency of complications decline with increasing age; however, protracted cough (> 3 months), sleep disturbances, and weight loss are common in adults with pertussis; subcutaneous emphysema, pulled muscles, and even broken ribs may occur in adults following paroxysmal coughing.11,12
In 2006 in the United States, infants younger than 6 months old had the highest reported rate of pertussis (84.21 per 100,000 population), but adolescents aged 10 to 19 years and adults older than 20 years contributed the greatest number of reported cases.4 The characteristic “whoop” is often absent in older individuals. It is not until the nagging, forceful cough has persisted for 2 or more weeks that adolescents and adults come to medical attention.13 Adult caretakers with undiagnosed pertussis are frequently found to be the source for pertussis in infants.14 Nosocomial spread by health care workers has been well documented.15,16
Bordetella are small, fastidious, aerobic gram-negative coccobacilli that require enriched media for isolation. B pertussis is a respiratory pathogen of humans only and is the sole cause of epidemic pertussis. B parapertussis is a closely related species that accounts for less than 5% of clinical pertussis.17B bronchiseptica occasionally causes disease in the immunocompromised host but is better recognized as a veterinary pathogen.18 Only B pertussiselaborates pertussis toxin.17,19 A variety of other components of B pertussis are biologically active as well as antigenic.
B pertussis attaches to ciliated epithelial cells of the respiratory tract, induces toxin-mediated ciliary paralysis and local inflammation, and decreases clearance of secretions. B pertussis is not invasive. Disease is mediated through a variety of bacterial components and toxins. Pertussis toxin is secreted by the bacteria and prevents migration of lymphocytes to the area of infection, inhibits the function of neutrophils, macrophages, monocytes, and lymphocytes. Bacterial adenylate cyclase toxin downregulates many immune cell functions and other cell-surface proteins, including filamentous hemagglutinin, pertactin (a 69-kd nonfimbrial protein), and fimbrial agglutinogens (FIM2, FIM3), promote bacterial attachment to ciliated respiratory epithelium. Tracheal cytotoxin destroys ciliated epithelial cells.19
The incubation period of pertussis is usually 5 to 10 days but may be up to 3 weeks. Clinical pertussis is a protracted illness with 3 identifiable stages: the catarrhal, the paroxysmal, and the convalescentstages. The catarrhal stage is the most contagious phase and is indistinguishable from a common cold. During this stage, fever is minimal or absent: rhinorrhea, sneezing, mild cough, and sometimes mild conjunctival suffusion last from a few days to a couple of weeks. In the young infant, signs and symptoms may be minimal or absent in the catarrhal stage.
Apnea, choking, or gasping may herald the paroxysmal stage in young infants.20-22 Observation in a setting in which assisted ventilation is available is prudent in the very young infant who presents with these features. Seemingly insignificant stimuli may provoke frightening episodes of coughing in the young infant, which may be sufficiently protracted to result in hypoxia and cyanosis. Forceful coughing can result in subconjunctival and scleral hemorrhages,23 upper-body petechiae, umbilical and inguinal hernias, subcutaneous emphysema, rib fractures, and even central nervous system hemorrhages.24 The characteristic inspiratory “whoop” of pertussis occurs in toddlers and older children at the end of a paroxysm as air is finally sucked in through a partially closed glottis. Posttussive emesis is common at all ages. Feeding becomes a major problem for the young infant and may actually provoke the paroxysm; the immediate postparoxysmal period may provide a refractory period during which feeding is possible. The severity of the child’s paroxysms contrasts sharply with the lack of distress seen between coughing spells. Most of the complications from pertussis occur in the paroxysmal stage, which may last from 1 to 6 weeks.
During the convalescent period, coughing in the young infant may actually become louder, although generally less distressing. Overall, the paroxysmal coughing gradually lessens in severity and frequency during convalescence. Paroxysms may disappear, only to reappear in a milder form during a subsequent respiratory illness over the ensuing year.
In addition to the immediate complications already mentioned, infectious and non-infectious complications of pertussis are numerous. Uncomplicated pertussis is usually an afebrile disease, so fever should prompt evaluation for a secondary bacterial infection. Otitis media and pneumonia are the most common secondary infections.12,25 Other pulmonary complications include atelectasis, emphysema, and pneumothorax. Coughing and vomiting may result in esophageal tears with hematemesis and melena. Neurologic complications include hypoxic encephalopathy, seizures, and intracranial bleeds.24-27Nutritional compromise and resultant failure to thrive is common in young infants recovering from pertussis. Risk of death in the young infant is between 0.04% and 1%.28
Classical pertussis should be readily diagnosed based on clinical features. The presence of absolute peripheral lymphocytosis (> 10,000 lymphocytes/mm3) is supportive evidence for systemically active pertussis toxin. Absolute lymphocyte counts of more than 20,000 cells/mm3 are not uncommon, and total WBC counts more than 100,000 cells/mm3 have been reported.
The chest x-ray in pertussis is often normal, although shagginess along the cardiac border, peribronchial consolidation, and atelectasis may be seen. The presence of a focal infiltrate in a febrile child with pertussis may indicate a secondary bacterial process.
Classic pertussis in the nonimmune host is difficult to confuse with other illnesses. In the immunized individual, symptoms are less likely to be characteristic. A coughing illness for more than 2 weeks and/or posttussive emesis should arouse suspicion. In infants presenting with apnea, respiratory syncytial virus infection and serious bacterial illness need to be excluded.
B pertussis is the cause of epidemic pertussis as well as of most sporadic pertussis. B parapertussis may cause a similar syndrome, which is less severe and of shorter duration. Protracted coughing illness mimicking pertussis may also be seen with adenovirus, mycoplasma, and chlamydia.29
Recovery of B pertussis in culture has long been the gold standard for the diagnosis of pertussis. Nasopharyngeal specimens should ideally be obtained within the first 2 to 3 weeks of illness, but cultures may be positive even weeks after the onset of paroxysms.8 Although the yield is less, cultures beyond 3 weeks are sometimes useful, because culture confirmation may guide public health initiatives.
Because of the fastidious growth requirements for B pertussis, cultures are most accurate in a laboratory experienced in B pertussis isolation. Nasopharyngeal samples should be obtained by inserting a small, flexible Dacron or calcium alginate swab through the nose into the posterior nasopharynx and leaving it there for a few seconds during a cough in order to gather respiratory epithelial cells.19,30-32 The best bacteriologic yield occurs when the swab is plated on selective Bordetella media at the bedside. If this is not possible, the swab should be placed in Bordetella-specific transport media for delivery to the laboratory. Prior antibiotic therapy will markedly reduce the isolation rate. Asymptomatic carriage of B pertussis is extremely rare. (Health-care workers collecting the specimens should use appropriate masks and eyewear to avoid becoming infected.)
A direct fluorescent antibody (DFA) test on secretions from a nasopharyngeal swab can be used for rapid presumptive diagnosis.30,32,33 In-experience in performing this test results in numerous false-positive and false-negative results, and thus DFA is not recommended by the CDC.30
Following infection, antibodies develop to several B pertussis antigens. These responses wane in 7 to 20 years.34 Serologic responses following immunization with pertussis vaccines last at least 6 to 12 years.35,36 Previous natural infection as well as immunization thus pose challenges to the serologic diagnosis of pertussis. Currently, the most generally accepted serologic criterion for diagnosis of pertussis is the use of an enzyme-linked immunosorbent assay to demonstrate a significant increase in IgG serum antibody concentrations against pertussis toxin between acute and convalescent specimens.19,37,38
Polymerase chain reaction (PCR) testing on nasopharyngeal swab specimens for pertussis is becoming the most widely used diagnostic procedure; however, techniques are not standardized.30,37 PCR has proven to be sensitive and specific for the diagnosis of pertussis and is an accepted alternative to culture for case confirmation of B pertussis infection when performed in experienced laboratories.31,39
Treatment for clinical pertussis is primarily supportive. Hospitalization is indicated for all infants with severe paroxysms associated with cyanosis or apnea. Infants with potentially fatal pertussis may appear to be amazingly well between paroxysms. Caution should be exercised when suctioning these young, exhausted infants because it may precipitate a paroxysm. Admission to an intensive care setting is indicated if emergent response to paroxysms cannot be managed on the ward. Supplemental oxygen, intravenous fluids, and nutritional support are frequently required in severe and protracted disease. Cough suppressants, expectorants, mucolytic agents, bronchial dilators, and sedatives are not beneficial in treating pertussis. Young infants should remain hospitalized until nutrition is adequate, no supportive intervention is required during paroxysms, disease is unchanged or improved for at least 48 hours, and the infant’s care can be safely managed at home.
Antibiotic therapy has no discernible effect on the course of the illness once the paroxysms are well established;7 however, treatment may ameliorate disease expression for those few who are treated in the catarrhal phase. Allsuspected and confirmed cases of pertussis should be treated in order to minimize secondary spread.41 Erythromycin at a dose of 40 to 50 mg/kg/day in 4 divided doses for 14 days (maximum, 250 mg 4 times a day); clarithromycin 15 mg/kg/day in 2 divided doses for 7 days; or azithromycin 10 mg/kg/day as single daily dose for 5 days are all recommended treatments.43 There are data demonstrating that 7 days of erythromycin estolate are as effective as 14 days, which may reflect the improved penetration of this erythromycin formulation over others.44 β-Lactam antibiotics are not effective against B pertussis.8
Household and daycare contacts of confirmed pertussis patients should receive antibiotic prophylaxis for 14 days after the last contact. Prophylaxis is indicated regardless of prior immunization status. Macrolides are the drugs of choice at the same dosages used for therapy.43 Efficacy of trimethoprim/sulfamethoxazole as a chemoprophylactic agent has not been evaluated.
B pertussis is highly contagious and has been recovered from the nasopharynx of infected individuals after 5 days of macrolide therapy. Therefore, hospitalized patients should be managed in respiratory isolation (droplet precautions) until 5 days after the initiation of macrolide therapy.30 A private room is preferred; however, culture-positive cases may be cohorted. Untreated patients should remain in isolation until 3 weeks after the onset of paroxysms. Local health officials should be notified of all cases in order to assist in outbreak control within the community. Immunization is the principal method of prevention. Immunization of infants, along with booster doses in preschool children, have been the mainstay of prevention. Recent introduction of routine immunization of adolescents and adults should have an impact on infant disease as well. Immunizations are discussed further in Chapter 244.