Emily Souder, Sarah S. Long
Pertussis is an acute respiratory tract infection; the term pertussis means “intense cough” and is preferable to whooping cough, because most infected individuals do not “whoop.”
Bordetella pertussis is the cause of epidemic pertussis and the usual cause of sporadic pertussis. Bordetella parapertussis is an occasional cause of sporadic pertussis that contributes significantly to total cases of pertussis in Eastern and Western Europe, but increasingly has been detected during regional pertussis outbreaks in the United States. B. pertussis and B. parapertussis are exclusive pathogens of humans and some primates. Bordetella holmesii , first identified as a cause of bacteremia in immunocompromised hosts without cough illness, also is reported to cause pertussis-like cough illness in small outbreaks in healthy persons. Bordetella bronchiseptica is a common animal pathogen. Occasional reports in humans describe a variety of body sites involved, and cases typically occur in immunocompromised persons or young children with intense exposure to animals. Protracted coughing (which in some cases is paroxysmal) is attributable sporadically to Mycoplasma, parainfluenza viruses, influenza viruses, enteroviruses, respiratory syncytial virus (RSV), or adenoviruses.
The World Health Organization (WHO) estimated that in 2008, 16 million cases of pertussis and 195,000 childhood deaths occurred worldwide, 95% of which were in developing countries. The WHO also estimated that 82% of infants worldwide received 3 doses of pertussis vaccine and that global vaccination against pertussis averted 687,000 deaths in 2008. Before vaccination was available, pertussis was the leading cause of death from communicable disease among U.S. children <14 yr old, with 10,000 deaths annually. Widespread use of whole cell pertussis vaccine (DTP) led to a >99% decline in cases. After the low U.S. number of 1,010 cases reported in 1976, there was an increase in annual pertussis incidence to 1.2 cases per 100,000 population from 1980 through 1989, with epidemic pertussis in many states in 1989–1990, 1993, and 1996. Since then, pertussis has become increasingly endemic, with shifting burden of disease to young infants, adolescents, and adults. By 2004, the incidence of reported pertussis in the United States was 8.9 cases per 100,000 in the general population and approximately 150 per 100,000 in infants <2 mo old, with 25,827 total cases reported, the highest since 1959. A total of 40 pertussis-related deaths were reported in 2005, and 16 were reported in 2006; >90% of these cases occurred in infants.
Prospective and serologic studies suggested that pertussis is underrecognized , especially among adolescents and adults, in whom the actual number of U.S. cases is estimated to be 600,000 annually. A number of studies documented pertussis in 13–32% of adolescents and adults with cough illness for >7 days. Responding to these changes in epidemiology, tetanus toxoid, reduced-content diphtheria toxoid, and acellular pertussis antigens (Tdap ) was recommended in 2006 for 11-12 yr olds and was aimed to enhance control. With >70% uptake of Tdap in adolescents, the burden of disease in young adolescents fell commensurately, but without evidence of protection of the community (herd) of young infants, older adolescents, and adults. An epidemiologic shift has occurred due to substantial and rapid waning of protection following both DTaP and Tdap in the aging cohort of children and adolescents who were not primed with DTP (whole cell) vaccine, which was no longer used in the United States after 1997. The >42,000 cases of pertussis and 20 deaths reported in 2012 were the highest numbers in >50 yr. A shift in disease burden was observed among 7-10 yr olds in 2010, 13-14 yr olds in 2012, and 14-16 yr olds in 2014, as the cohort of solely DTaP-vaccinated cohort aged.
Neither natural disease nor vaccination provides complete or lifelong immunity against pertussis reinfection or disease. Subclinical reinfection undoubtedly contributed significantly to immunity against disease ascribed previously to both vaccine and prior infection. The resurgence of pertussis can be attributed to a variety of factors, including partial control of pertussis leading to less continuous exposure as well as increased awareness and improved diagnostics. Rapidly waning vaccine-induced immunity and pathogen adaptation are most important currently. Although the DTaP series is protective short-term, vaccine effectiveness wanes rapidly, with estimates of only 10% protection 8.5 yr after the 5th dose. Tdap protection also is short-lived, with efficacy falling from >70% initially to 34% within 2-4 yr. Divergence of circulating strains from vaccine strains began with the introduction of DTP, but with the exclusive use of acellular pertussis vaccines, pertactin-deficient strains emerged and have become dominant in countries where these vaccines are used. Pertactin-deficient B. pertussis was first reported in the United States from a Philadelphia infant case collection from 2008 to 2011. The Centers for Disease Control and Prevention (CDC) subsequently reported the earliest U.S. isolate from 1994 and rapid dominance of pertactin-deficient strains in the United States since 2010. Despite the role of pertactin as a bacterial virulence factor, illness severity in infants with pertactin-deficient B. pertussis is similar to that of pertactin-producing strains. Until development of new pertussis vaccine(s), pertussis will continue to be endemic, with cycling epidemics.
Bordetella organisms are small, fastidious, gram-negative coccobacilli that colonize only ciliated epithelium. The exact mechanism of disease symptomatology remains unknown. Bordetella species share a high degree of DNA homology among virulence genes. Only B. pertussis expresses pertussis toxin (PT), the major virulence protein. PT has numerous proven biologic activities (e.g., histamine sensitivity, insulin secretion, leukocyte dysfunction). Injection of PT in experimental animals causes lymphocytosis immediately by rerouting lymphocytes to remain in the circulating blood pool but does not cause cough. PT appears to have a central, but not a singular, role in pathogenesis. B. pertussis produces an array of other biologically active substances, many of which are postulated to have a role in disease and immunity. After aerosol acquisition, filamentous hemagglutinin , some agglutinogens (especially fimbriae [Fim] types 2 and 3), and the 69-kDa pertactin (Prn) protein are important for attachment to ciliated respiratory epithelial cells. Tracheal cytotoxin, adenylate cyclase, and PT appear to inhibit clearance of organisms. Tracheal cytotoxin, dermonecrotic factor, and adenylate cyclase are postulated to be predominantly responsible for the local epithelial damage that produces respiratory symptoms and facilitates absorption of PT. Both antibody and cellular immune responses follow infection and immunization. Antibody to PT neutralizes toxin, and antibody to Prn enhances opsonophagocytosis. Disease as well as DTP appear to drive a mixed cellular and antibody (Th1) immunologic response, while DTaP and Tdap drive a narrow antibody-dominant (Th2) response.
Pertussis is extremely contagious , with attack rates as high as 100% in susceptible individuals exposed to aerosol droplets at close range. High airborne transmission rates were shown in a baboon model of pertussis despite vaccination with the acellular vaccine. B. pertussis does not survive for prolonged periods in the environment. Chronic carriage by humans is not documented. After intense exposure as in households, the rate of subclinical infection is as high as 80% in fully immunized or previously infected individuals. When carefully sought, a symptomatic source case can be found for most patients; usually a sibling or related adult.
Classically, pertussis is a prolonged disease, divided into catarrhal, paroxysmal, and convalescent stages. The catarrhal stage (1-2 wk) begins insidiously after an incubation period ranging from 3-12 days with nondistinctive symptoms of congestion and rhinorrhea variably accompanied by low-grade fever, sneezing, lacrimation, and conjunctival suffusion. As initial symptoms wane, coughing marks the onset of the paroxysmal stage (2-6 wk). The cough begins as a dry, intermittent, irritative hack and evolves into the inexorable paroxysms that are the hallmark of pertussis. A well-appearing, playful toddler with insignificant provocation suddenly expresses an anxious aura and may clutch a parent or comforting adult before beginning a machine-gun burst of uninterrupted cough on a single exhalation, chin and chest held forward, tongue protruding maximally, eyes bulging and watering, face purple, until coughing ceases and a loud whoop follows as inspired air traverses the still partially closed airway. Posttussive emesis is common, and exhaustion is universal. The number and severity of paroxysms escalate over days to a week and remain at that plateau for days to weeks. At the peak of the paroxysmal stage, patients may have >1 episode hourly. As the paroxysmal stage fades into the convalescent stage (≥2 wk), the number, severity, and duration of episodes diminish.
Infants <3 mo old do not display the classic stages. The catarrhal phase lasts only a few days or is unnoticed, and then, after the most insignificant startle from a draft, light, sound, sucking, or stretching, a well-appearing young infant begins to choke, gasp, gag, and flail the extremities, with face reddened. Cough may not be prominent, especially in the early phase, and whoop is infrequent. Apnea and cyanosis can follow a coughing paroxysm, or apnea can occur as the only symptom (without cough). Both are more common with pertussis than with neonatal viral infections. The paroxysmal and convalescent stages in young infants are lengthy. Paradoxically, in infants, cough and whooping may become louder and more classic in convalescence. “Exacerbations” of paroxysmal coughing can occur throughout the 1st yr. of life with subsequent respiratory illnesses; these are not a result of recurrent infection or reactivation of B. pertussis.
Adolescents and previously immunized children have foreshortening of all stages of pertussis. Adults have no distinct stages. Classically, adolescents and adults describe a sudden feeling of strangulation followed by uninterrupted coughs, feeling of suffocation, bursting headache, diminished awareness, and then a gasping breath, usually without a whoop. Posttussive emesis and intermittency of paroxysms separated by hours of well-being are specific clues to the diagnosis. At least 30% of adolescents and adults with pertussis have nonspecific cough illness, distinguished only by duration, which usually is >21 days.
Findings on physical examination generally are uninformative. Signs of lower respiratory tract disease are not expected unless complicating secondary bacterial pneumonia is present. Conjunctival hemorrhages and petechiae on the upper body are common.
Pertussis should be suspected in any individual who has a pure or predominant complaint of cough, especially if the following features are absent : fever, malaise or myalgia, exanthem or enanthem, sore throat, hoarseness, tachypnea, wheezes, and rales. For sporadic cases, a clinical case definition of cough of ≥14 days’ duration with at least 1 associated symptom of paroxysms, whoop, or posttussive vomiting has sensitivity of 81% and specificity of 58% for confirmation of pertussis. Pertussis should be suspected in older children whose cough illness is escalating at 7-10 days and whose coughing is not continuous, but rather comes in bursts. Pertussis should be suspected in infants <3 mo old with gagging, gasping, apnea, cyanosis, or an apparent life-threatening event. Sudden infant death occasionally is caused by B. pertussis .
Adenoviral infections usually are distinguishable by associated features, such as fever, sore throat, and conjunctivitis. Mycoplasma causes protracted episodic coughing, but patients usually have a history of fever, headache, and systemic symptoms at the onset of disease as well as more continuous cough and frequent finding of rales on auscultation of the chest. Epidemics of Mycoplasma and B. pertussis in young adults can be difficult to distinguish on clinical grounds. Although pertussis often is included in the differential diagnosis of young infants with afebrile pneumonia, B. pertussis is not associated with staccato cough (breath with every cough), purulent conjunctivitis, tachypnea, rales or wheezes that typify infection by Chlamydia trachomatis, or predominant lower respiratory tract signs that typify infection by RSV. Unless an infant with pertussis has secondary pneumonia (and then appears ill), the findings on examination between paroxysms, including respiratory rate, are entirely normal. Foreign body aspiration should be considered in the differential diagnosis.
Leukocytosis (15,000-100,000 cells/µL) caused by absolute lymphocytosis is characteristic in the catarrhal stage. Lymphocytes are normal small cells, rather than the large, atypical lymphocytes seen with viral infections. Adults, partially immune children, and occasionally infants may have less impressive lymphocytosis. Absolute increase in neutrophils suggests a different diagnosis or secondary bacterial infection. Eosinophilia is not a manifestation of pertussis. A severe course and death are correlated with rapid-rise and extreme leukocytosis (median peak white blood cell count in fatal vs nonfatal cases, 94,000 vs 18,000/µL, respectively) and thrombocytosis (median peak platelet count in fatal vs nonfatal cases, 782,000 vs 556,000/µL, respectively). Chest radiographic findings are only mildly abnormal in the majority of hospitalized infants, showing perihilar infiltrate or edema (sometimes with a butterfly appearance) and variable atelectasis. Parenchymal consolidation suggests secondary bacterial infection. Pneumothorax, pneumomediastinum, and subcutaneous emphysema can be seen occasionally.
Methods for confirmation of infection by B. pertussis (culture, PCR, serology) have limitations in sensitivity, specificity, or practicality, and tests’ relative values depend on the setting, phase of disease, and purpose of use (e.g., as clinical diagnostic vs epidemiologic tools). Polymerase chain reaction (PCR) testing on nasopharyngeal wash specimens is the laboratory test of choice for B. pertussis identification. Both stand-alone and multiplex assays are U.S. Food and Drug Administration (FDA) cleared and available commercially. PCR assays using only single primers (IS481 ) cannot differentiate between some Bordetella spp. Multiplex assays using multiple targets can distinguish species. All assays detect pertactin-deficient strains. For culture , a specimen is obtained by deep nasopharyngeal aspiration or with the use of a flexible swab (Dacron or calcium alginate–tipped), held in the posterior nasopharynx for 15-30 sec (or until cough occurs). A 1% casamino acid liquid is acceptable for holding a specimen up to 2 hr; Stainer-Scholte broth or Regan-Lowe semisolid transport medium is used for longer transport periods, up to 4 days. The preferred isolation media are Regan-Lowe charcoal agar with 10% horse blood and 5-40 µg/mL cephalexin, and Stainer-Scholte media with cyclodextrin resins. Cultures are incubated at 35-37°C in a humid environment and examined daily for 7 days for slow-growing, tiny, glistening colonies. Direct fluorescent antibody testing of potential isolates using specific antibody for B. pertussis and B. parapertussis maximizes recovery rates.
Results of culture and PCR are expected to be positive in unimmunized, untreated children during the catarrhal and early paroxysmal stages of disease. However, fewer than 20% of culture or PCR tests have positive results in partially or remotely immunized individuals tested in the paroxysmal stage. Serologic tests for detection of change in antibodies to B. pertussis antigens between acute and convalescent samples are the most sensitive tests in immunized individuals and are useful epidemiologically. A single serum sample showing IgG antibody to PT >90 IU/mL (>2 SD above the mean of the immunized population) indicates recent symptomatic infection and usually is positive in the mid-paroxysmal phase. Tests for IgA and IgM pertussis antibody, or antibody to antigens other than PT, are not reliable methods for serologic diagnosis of pertussis.
Infants <3 mo old with suspected pertussis usually are hospitalized, as are many 3-6 mo old, unless witnessed paroxysms are not severe, as well as patients of any age if significant complications occur. Prematurely born young infants have a high risk for severe, potentially fatal disease, and children with underlying cardiac, pulmonary, muscular, or neurologic disorders have increased risk of poor outcome beyond infancy. Table 224.1 lists caveats in assessment and care of infants with pertussis. The specific, limited goals of hospitalization are to (1) assess progression of disease and likelihood of life-threatening events at peak of disease; (2) maximize nutrition; (3) prevent or treat complications; and (4) educate parents in the natural history of the disease and in care that will be given at home. Heart rate, respiratory rate, and pulse oximetry are monitored continuously with alarm settings so that paroxysms can be witnessed and recorded by healthcare personnel. Detailed cough records and documentation of feeding, vomiting, and weight change provide data to assess severity. Typical paroxysms that are not life threatening have the following features: duration <45 sec; red but not blue color change; tachycardia, bradycardia (not <60 beats/min in infants), or oxygen desaturation that spontaneously resolves at the end of the paroxysm; whooping or strength for brisk self-rescue at the end of the paroxysm; self-expectorated mucus plug; and posttussive exhaustion but not unresponsiveness. Assessing the need to provide oxygen, stimulation, or suctioning requires skilled personnel who can watchfully observe an infant's ability for self-rescue but who will intervene rapidly and expertly when necessary. The benefit of a quiet, dimly lighted, undisturbed, comforting environment cannot be overestimated or forfeited in a desire to monitor and intervene. Feeding children with pertussis is challenging. The risk of precipitating cough by nipple feeding does not warrant nasogastric, nasojejunal, or parenteral alimentation in most infants. The composition or thickness of formula does not affect the quality of secretions, cough, or retention. Large-volume feedings are avoided.
Table 224.1
Caveats in Assessment and Care of Infants With Pertussis
Within 48-72 hr, the direction and severity of disease are obvious from analysis of recorded information. Hospital discharge is appropriate if, over 48 hr, disease severity is unchanged or diminished, intervention is not required during paroxysms, nutrition is adequate, no complication has occurred, and parents are adequately prepared for care at home. Apnea and seizures occur in the incremental phase of illness and in patients with complicated disease. Portable oxygen, monitoring, or suction apparatus should not be needed at home.
Infants who have apnea, paroxysms that lead to life-threatening events, or respiratory failure require escalating respiratory support and frequently require intubation and pharmaceutically induced paralysis.
An antimicrobial agent always is given when pertussis is suspected or confirmed to decrease contagiousness and to afford possible clinical benefit. Azithromycin is the drug of choice in all age-groups, for treatment or postexposure prophylaxis (Table 224.2 ). Macrolide resistance has been reported rarely, and recent isolates have retained susceptibility despite genetic strain adaptations. Infantile hypertrophic pyloric stenosis (IHPS) is associated with macrolide use in young infants, especially in those <14 days old, with highest risk in those receiving erythromycin vs azithromycin. Benefits of postexposure prophylaxis or treatment of infants far outweigh risk of IHPS. Young infants should be managed expectantly if projectile vomiting occurs. The FDA also warns of risk of fatal heart rhythms with use of azithromycin in patients already at risk for cardiovascular events, especially those with prolongation of the QT interval. Trimethoprim-sulfamethoxazole (TMP-SMX) is an alternative to azithromycin for infants >2 mo old and children unable to receive azithromycin. Because of limited effectiveness, treatment of B. parapertussis is based on clinical judgment and is considered in high-risk populations. Agents are the same as for B. pertussis . Treatment of infections caused by other Bordetella spp. should be undertaken with consultation of a subspecialist.
Table 224.2
Recommended Antimicrobial Treatment and Postexposure Prophylaxis for Pertussis
| AGE-GROUP | PRIMARY AGENTS | ALTERNATE AGENT* | ||
|---|---|---|---|---|
| Azithromycin | Erythromycin | Clarithromycin | TMP-SMX | |
| <1 mo |
Recommended agent 10 mg/kg/day in a single dose for 5 days |
Not preferred Erythromycin is substantially associated with infantile hypertrophic pyloric stenosis. Use if azithromycin is unavailable; 40-50 mg/kg/day in 4 divided doses for 14 days. |
Not recommended (safety data unavailable) | Contraindicated for infants <2 mo of age (risk for kernicterus) |
| 1-5 mo | 10 mg/kg/day in a single dose for 5 days | 40-50 mg/kg/day in 4 divided doses for 14 days | 15 mg/kg/day in 2 divided doses for 7 days |
Contraindicated at age <2 mo For infants age ≥2 mo: TMP 8 mg/kg/day plus SMX 40 mg/kg/day in 2 divided doses for 14 days |
| Infants age ≥6 mo and children | 10 mg/kg in a single dose on day 1 (max 500 mg), then 5 mg/kg/day (max 250 mg) on days 2-5 | 40-50 mg/kg/day (max 2 g/day) in 4 divided doses for 14 days | 15 mg/kg/day in 2 divided doses (max 1 g/day) for 7 days | TMP 8 mg/kg/day plus SMX 40 mg/kg/day in 2 divided doses (max TMP: 320 mg/day) for 14 days |
| Adults | 500 mg in a single dose on day 1, then 250 mg/day on days 2-5 | 2 g/day in 4 divided doses for 14 days | 1 g/day in 2 divided doses for 7 days | TMP 320 mg/day–SMX 1600 mg/day in 2 divided doses for 14 days |
* Trimethoprim-sulfamethoxazole (TMP-SMX) can be used as an alternative agent to macrolides in patients ≥2 mo old who are allergic to macrolides, who cannot tolerate macrolides, or who are infected with a rare macrolide-resistant strain of Bordetella pertussis .
Adapted from Centers for Disease Control and Prevention (CDC): Recommended antimicrobial agents for treatment and postexposure prophylaxis of pertussis: 2005 CDC guidelines, MMWR 54:1–16, 2005.
No rigorous clinical trial has demonstrated a beneficial effect of β2 -adrenergic stimulants such as salbutamol and albuterol. Fussing associated with aerosol treatment triggers paroxysms. No randomized, blinded clinical trial of sufficient size has been performed to evaluate the usefulness of corticosteroids in the management of pertussis; their clinical use is not warranted. A randomized, double-blind, placebo-controlled trial of pertussis immunoglobulin intravenous (IGIV) was halted prematurely because of expiration/lack of additional supply of study product; there was no indication of clinical benefit. Standard immunoglobulin has not been studied and should not be used for treatment or prophylaxis.
Patients with suspected pertussis are placed in isolation with droplet precautions to reduce close respiratory or mucous membrane contact with respiratory secretions. All healthcare personnel should wear a mask on entering the room. Screening for cough should be performed on entrance of patients to emergency departments, offices, and clinics to begin isolation immediately and until 5 days after initiation of azithromycin therapy. Children and staff with pertussis in childcare facilities or schools should be excluded until therapy has been taken for 5 days.
Azithromycin should be given promptly to all household contacts and other close contacts, such as those in daycare, regardless of age, history of immunization, or symptoms (see Table 224.2 ). The same drugs and age-related doses used for treatment are used for prophylaxis. Visitation and movement of coughing family members in the hospital must be assiduously controlled until therapy has been taken for 5 days. In close contacts <7 yr old who have received <4 doses of DTaP, DTaP should be given to complete the recommended series. Children <7 yr old who received a 3rd DTaP dose >6 mo before exposure, or a 4th dose ≥3 yr before exposure, should be given a booster dose. Individuals ≥9 yr old should be given Tdap. Unmasked healthcare personnel exposed to untreated cases should be evaluated for postexposure prophylaxis and follow-up. Coughing healthcare personnel with or without known exposure to pertussis should be evaluated promptly for pertussis.
Infants <6 mo old have excessive mortality and morbidity; infants <2 mo old have the highest reported rates of pertussis-associated hospitalization (82%), pneumonia (25%), seizures (4%), encephalopathy (1%), and death (1%). Infants <4 mo old account for 90% of cases of fatal pertussis. Preterm birth and young maternal age are significantly associated with fatal pertussis. Neonates with pertussis have substantially longer hospitalizations, greater need for oxygen, and greater need for mechanical ventilation than neonates with viral respiratory tract infection.
The principal complications of pertussis are apnea , secondary infections (e.g., otitis media, pneumonia), and physical sequelae of forceful coughing. Fever, tachypnea or respiratory distress between paroxysms and absolute neutrophilia are clues to pneumonia. Expected pathogens include Staphylococcus aureus, Streptococcus pneumoniae, and bacteria of oropharyngeal flora. Increased intrathoracic and intraabdominal pressure during coughing can result in conjunctival and scleral hemorrhage, petechiae on the upper body, epistaxis, pneumothorax and subcutaneous emphysema, umbilical or inguinal hernia, and rarely hemorrhage in the central nervous system or retina. Laceration of the lingual frenulum occurs occasionally.
The need for intensive care and mechanical ventilation usually is limited to infants <3 mo old and children with underlying conditions. Respiratory failure from apnea may mandate intubation and ventilation through the days when disease peaks; prognosis is good. Progressive pulmonary hypertension in very young infants and secondary bacterial pneumonia are severe complications of pertussis and are the usual causes of death. Pulmonary hypertension and cardiogenic shock with fatal outcome are associated with extreme elevation of lymphocyte and platelet counts. Autopsies in fatal cases show luminal aggregates of leukocytes in the pulmonary vasculature. Extracorporeal membrane oxygenation of infants with pertussis in whom mechanical ventilation failed has been associated with >80% fatality (questioning the advisability of this procedure). Exchange transfusion or leukapheresis is associated with marked reduction in lymphocyte and platelet counts. Although recovery has been reported in several cases, benefit is unproven. Echocardiography should be performed in critically ill infants with pertussis to detect presence of pulmonary hypertension and to intervene expeditiously.
Acute neurologic events during pertussis almost always are the result of hypoxemia or hemorrhage associated with coughing or apnea in young infants. Apnea or bradycardia or both may result from apparent laryngospasm or vagal stimulation just before a coughing episode, from obstruction during an episode, or from hypoxemia following an episode. Seizures usually are a result of hypoxemia, but hyponatremia from excessive secretion of antidiuretic hormone during pneumonia can occur. The only neuropathology documented in pertussis is parenchymal hemorrhage and ischemic necrosis.
Bronchiectasis has been reported rarely after pertussis. Children who have pertussis before age 2 yr may have abnormal pulmonary function into adulthood.
Universal immunization of children with pertussis vaccine, beginning in infancy with reinforcing dose(s) through adolescence and adulthood, is central to the control of pertussis. Prevention of pertussis mortality in young infants depends on universal maternal immunization during each pregnancy and focused full immunization of contacts, both children and adults of all ages.
Several diphtheria and tetanus toxoids combined with acellular pertussis vaccines (DTaP ) or combination products currently are licensed in the United States for children <7 yr old. Acellular pertussis vaccines all contain inactivated PT and 2 or more additional antigens (filamentous hemagglutinin, Prn, and Fim 2 and 3). Clinical effectiveness immediately at completion of the 5-dose series is approximately 80% for illness defined as “paroxysmal cough” for >21 days. Mild local and systemic adverse events are not uncommon, but more serious events (persistent crying for ≥3 hr, hypotonic hyporesponsive episodes, seizures) are rare. DTaP-containing vaccines can be administered simultaneously with any other vaccines used in the standard schedule for children.
Four doses of DTaP should be administered during the 1st 2 yr of life, generally at ages 2, 4, 6, and 15-18 mo. In high-risk settings, infants may be given DTaP as early as 6 wk of age, with monthly doses through the 3rd dose. The 4th dose may be administered as early as 12 mo of age, provided that 6 mo have elapsed since the 3rd dose. When feasible, the same DTaP product is recommended for all doses of the primary vaccination series. The 5th dose of DTaP is recommended for children at 4-6 yr of age; a 5th dose is not necessary if the 4th dose in the series is administered on or after the 4th birthday.
Local reactions increase modestly in rate and severity with successive doses of DTaP. Swelling of the entire thigh or upper arm, sometimes accompanied by pain, erythema, and fever, has been reported in 2–3% of vaccinees after the 4th or 5th dose of a variety of DTaP products. Limitation of activity is less than might be expected. Swelling subsides spontaneously without sequelae. The pathogenesis is unknown. Extensive limb swelling after the 4th dose of DTaP usually is not associated with a similar reaction to the 5th dose and is not a contraindication to subsequent dose(s) of pertussis vaccines.
Exempting children from pertussis immunization should be considered only within the narrow limits as recommended. Exemptors have significantly increased risk for pertussis and play a role in outbreaks of pertussis among immunized populations. Although well-documented pertussis confers short-term protection, the duration of protection is unknown; immunization should be completed on schedule in children diagnosed with pertussis.
Two tetanus toxoid, reduced-diphtheria toxoid and acellular pertussis antigen vaccine (Tdap) products were licensed in 2005 and recommended universally in 2006 for adolescents. The preferred age for Tdap vaccination is 11-12 yr. All adolescents and adults of any age (including ≥65 yr) who have not received Tdap should receive a single dose of Tdap promptly, regardless of interval since Td, or at least in place of one Td booster at the 10 yr interval, or when indicated during wound management.
Pregnant women should be given Tdap during every pregnancy to provide passive antibody protection to the infant until administration of DTaP. Although Tdap can be given at any time during pregnancy, optimal administration is early in the period between 27 and 36 wk of gestation to maximize antibody concentration at birth. Safety of Tdap during pregnancy and effectiveness in reducing fatal pertussis in infants are proven. Special effort should be made to ensure that contacts of infants have received DTaP or Tdap as recommended. There is no recommendation for Tdap revaccination of persons other than pregnant women. Although no safety issues are associated with Tdap revaccination, rapidly waning protection following receipt of currently available vaccines does not support cost-effectiveness of universal revaccination.
There is no contraindication to concurrent administration of any other indicated vaccine. When Td is indicated and only Tdap is available, a previously Tdap-immunized person can be given Tdap. A single dose of Tdap is recommended for children 7-10 yr old who had incomplete DTaP vaccination before age 7 yr. Another dose of Tdap can be given in adolescence.