Pertussis (Bordetella Pertussis and Bordetella Parapertussis)

Transcription

1 Pertussis (Bordetella Pertussis and Bordetella Parapertussis) Sarah S. Long Pertussis is an acute respiratory tract infection that was well described initially in the 1500s. Sydenham first used the term pertussis, meaning intense cough, in 1670; it is preferable to whooping cough because most infected individuals do not whoop. ETIOLOGY. Bordetella pertussis is the sole 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 accounts for <5% of Bordetella isolates in the United States. B. pertussis and B. parapertussis are exclusive pathogens of humans and some primates. B. bronchiseptica is a common animal pathogen. Occasional case reports in humans may involve any body site and typically occur in immunocompromised persons or young children with intense exposure to animals. Protracted coughing can be caused by Mycoplasma, parainfluenza or influenza viruses, enteroviruses, respiratory syncytial virus, or adenoviruses. None of these is an important cause of pertussis. EPIDEMIOLOGY. There are 60 million cases of pertussis each year worldwide, resulting in >500,000 deaths. Before vaccination was available, pertussis was the leading cause of death due to communicable disease among children <14 yr of age in the United States, with 10,000 deaths annually. Widespread use of pertussis vaccine led to a >99% decline in cases. The pivotal role of vaccination in disease control is reflected in the continued high incidence of pertussis in developing countries,

2 and resurgence in other countries where vaccine coverage is low or where less potent vaccine may have been used. After the low number of 1,010 cases in the United States reported in 1976, there was an increase in annual pertussis incidence to 1.2 cases/100,000 population from 1980 through 1989 with epidemic pertussis in many states in , 1993, and Pertussis is increasingly endemic, with less cycling or seasonality than previously occurred. In 2004, incidence of reported pertussis in the United States increased for the 3rd year in a row, to 8.9 cases per 100,000 population, more than twice the rate reported in 2003 and an increase from 1.8 in The number of cases (25,827) was the highest reported since Of these, 10% occurred among infants <6 mo of age who were too young to have received the 1st 3 of the 5 doses of vaccine that are recommended by 6 yr of age. This age group had the highest reported rate, 136.5/100,000 population. Infants have the highest morbidity associated with pertussis, although adolescents and adults now account for the majority (67%) of reported cases as vaccine-induced immunity wanes and they become susceptible to infection. Approximately 60% of cases are in adolescents and adults. Pertussis is the only vaccine-preventable disease for which universal immunization in the United States is recommended that continues to show rising incidence. There is good evidence that the diagnosis of pertussis is underconsidered, underproven, and underreported. Pertussis is extremely contagious, with attack rates as high as 100% in susceptible individuals exposed to aerosol droplets at close range. 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, however, a symptomatic source case can be found for most patients. Neither natural disease nor vaccination provides complete or lifelong immunity against reinfection or disease. Protection against typical disease begins to wane 3 5 yr after vaccination and is unmeasurable after 12 yr. Subclinical reinfection undoubtedly has contributed significantly to immunity against disease ascribed previously to both vaccine and prior infection. Adolescents and adults in the United States have inadequate antibody to B. pertussis. Despite history of disease or complete immunization, outbreaks of pertussis have occurred in the elderly, in nursing homes, in residential facilities with

3 limited exposures, in highly immunized suburbia, and in preadolescents, adolescents, and adults with lapsing time since immunization. Coughing adolescents and adults (usually not recognized as having pertussis) currently are the major reservoir for B. pertussis and are the usual sources for index cases in infants and children. In the prevaccine era and in countries such as Germany, Sweden, and Italy, where immunization was limited, the peak incidence of pertussis is in children 1 5 yr of age; infants account for <15% of cases. In the USA in 2003, the highest incidence of pertussis was in infants <6 mo of age (approximately 2,000 cases; 80 cases per 100,000 population), but the largest number of cases occurred among children and adolescents yr of age (2,600 cases) and yr of age (1,800 cases). A number of studies have documented pertussis in 13 32% of adolescents and adults with cough illness for >7 days. It is estimated that at least 1 million individuals have such B. pertussis infections annually in the USA. Possible explanations for change in epidemiology include waning immunity postimmunization, an aging cohort who received less effective vaccine, and increased awareness and diagnosis. Without natural reinfection with B. pertussis or repeated booster vaccinations, adolescents and adults are susceptible to clinical disease if exposed, and mothers provide little if any passive protection to young infants. PATHOGENESIS. Bordetella organisms are tiny, fastidious, gram-negative coccobacilli that only colonize ciliated epithelium. 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), some of which may account for systemic manifes tations of disease. PT causes lymphocytosis immediately in experimental animals by rerouting lymphocytes to remain in the circulating blood pool. 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

4 immunity. After aerosol acquisition, filamentous hemagglutinin (FHA), some agglutinogens (especially fimbriae [Fim] types 2 and 3), and a 69 kd nonfimbrial surface protein called pertactin (Pn) 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. CLINICAL MANIFESTATIONS. 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 coughs, 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. Post-tussive 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 more than 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 of age do not display classical stages. The catarrhal phase lasts only a few days or is unnoticed when 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 extremities, with face

5 reddened. Cough (expiratory grunt) may not be prominent. Whoop infrequently occurs in infants <3 mo of age who at the end of a paroxysm lack stature or muscular strength to create sudden negative intrathoracic pressure. Cyanosis can follow a coughing paroxysm, or apnea can occur without a cough. Apnea may be the only symptom. The paroxysmal and convalescent stages in young infants are lengthy. Paradoxically, in infants, cough and whooping may become louder and more classic in convalescence. Convalescence includes intermittent paroxysmal coughing throughout the 1st year of life, including exacerbations with subsequent respiratory illnesses; these are not due to recurrent infection or reactivation of B. pertussis. Immunized children have foreshortening of all stages of pertussis. Adults have no distinct stages. Classically, 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. Post-tussive emesis and intermittency of paroxysms separated by hours of wellbeing are specific clues to the diagnosis in adolescents and adults. In prospective studies, at least ⅓ of older individuals with pertussis have nonspecific cough illness, distinguished only by duration, which is usually >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. DIAGNOSIS. Pertussis should be suspected in any individual who has pure or predominant complaint of cough, especially if the following are absent: fever, malaise or myalgia, exanthem or enanthem, sore throat, hoarseness, tachypnea, wheezes, and rales. For sporadic

6 cases, a clinical case definition of cough of 14 days' duration with at least 1 associated symptom of paroxysms, whoop, or post-tussive vomiting has a sensitivity of 81% and specificity of 58% for culture confirmation. Pertussis should be suspected in older children whose cough illness is escalating at 7 10 days and whose coughing episodes are not continuous. Pertussis should be suspected in infants <3 mo of age with apnea, cyanosis, or an acute lifethreatening event (ALTE). B. pertussis is an occasional cause of sudden infant death. Adenoviral infections are usually 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 is often included in the laboratory evaluation 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 due to Chlamydia trachomatis, or predominant lower respiratory tract signs that typify infection due to respiratory syncytial virus. Unless an infant with pertussis has secondary pneumonia (and is then ill appearing), the findings on examination between paroxysms are entirely normal, including respiratory rate. Leukocytosis (15, ,000 cells/mm3) due to absolute lymphocytosis is characteristic in the catarrhal stage. Lymphocytes are of T- and B-cell origin and are normal small cells, rather than the large atypical lymphocytes seen with viral infections. Adults, partially immune children, and occasionally young infants 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 extreme leukocytosis (median peak white blood cell count fatal vs nonfatal cases, 94 vs cells/l) and thrombocytosis (median peak platelet count fatal vs nonfatal cases, 782 vs /L). Mild hyperinsulinemia and reduced glycemic response to epinephrine have been demonstrated, although hypoglycemia is reported only occasionally. The chest x-ray is only mildly abnormal in the majority of hospitalized infants, showing

7 perihilar infiltrate or edema (sometimes with a butterfly appearance) and variable atelectasis. Parenchymal consolidation suggests secondary bacterial infection. Pneumothorax, pneumomediastinum, and air in soft tissues can be seen occasionally. All current methods for confirmation of infection due to B. pertussis have limitations in sensitivity, specificity, or practicality. Isolation of B. pertussis in culture remains the gold standard for diagnosis. Careful attention must be directed to specimen collection, transport, and isolation technique. The specimen is obtained by deep nasopharyngeal aspiration or by use of a flexible swab, preferably a dacron or calcium alginate swab, held in the posterior nasopharynx for sec (or until coughing). A 1.0% 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 periods, up to 4 days. Regan-Lowe charcoal agar with 10% horse blood and 5 40 µg/ml cephalexin or Stainer-Scholte media with cyclodextrin resins are the preferred isolation media. Cultures are incubated at F in a humid environment and examined daily for 7 days for slow-growing, tiny, glistening colonies. Direct fluorescent antibody (DFA) testing of potential isolates using specific antibody for B. pertussis and B. parapertussis maximizes recovery. Direct testing of nasopharyngeal secretions by DFA is a rapid test, but is reliable only in laboratories with continuous experience. Polymerase chain reaction (PCR) to test nasopharyngeal wash specimens has a sensitivity similar to that of culture, averts difficulties of isolation, but is not standardized or available universally. Results of DFA, culture, and PCR are all expected to be positive in unimmunized, untreated children during the catarrhal and early paroxysmal stage of disease. Less than 10% of any of these test results are positive in partially or remotely immunized individuals tested in the paroxysmal stage. Serologic tests for detection of antibodies to B. pertussis antigens in acute and convalescent samples are the most sensitive tests in immunized individuals and are useful epidemiologically. A single serum sample showing immunoglobulin G (IgG) antibody to pertussis toxin elevated >2 standard deviations above the mean of the immunized population indicates recent infection. Standardization of tests and cut point for a positive result are currently being investigated. IgA and IgM pertussis antibody tests are not reliable methods for diagnosis. TREATMENT.

8 Goals of therapy are to limit the number of paroxysms, to observe the severity of the cough, to provide assistance when necessary, and to maximize nutrition, rest, and recovery without sequelae ( Table ). Infants <3 mo of age are admitted to hospital almost without exception, as are those between 3 6 mo unless witnessed paroxysms are not severe, and those of any age if significant complications occur. Prematurely born young infants and children with underlying cardiac, pulmonary, muscular, or neurologic disorders have a high risk for severe disease. TABLE Caveats in Assessment and Care of Infants with Pertussis Infants with potentially fatal pertussis may appear well between episodes. A paroxysm must be witnessed before deciding between hospital and home care. Only analysis of carefully compiled cough record permits assessment of severity and progression of illness. Suctioning of nose, oropharynx, or trachea should not be performed on a preventive schedule. Feeding in the period following a paroxysm may be more successful than following napping. Family support begins at the time of hospitalization with empathy for the child's and family's experience to date, transfer of the burden of responsibility for the child's safety to the health care team, and delineation of assessments and treatments to be performed. Family education, recruitment as part of the team, and continued support after discharge are essential. The specific, limited goals of hospitalization are to (1) assess progression of disease and likelihood of lifethreatening events at peak of disease, (2) prevent or treat complications, and (3) educate parents in the natural history of the disease and in care that will be given at

9 home. Heart rate, respiratory rate, and pulse oximetry are monitored continuously with alarm settings so that paroxysms can be witnessed and recorded by health care 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 self-rescue at the end of the paroxysm; self-expectorated mucus plug; and post-tussive exhaustion but not unresponsiveness. Assessing the need to provide oxygen, stimulation, or suctioning requires skilled personnel who can document an infant's ability for self-rescue but who will intervene rapidly and expertly when necessary. Infants whose paroxysms repeatedly lead to life-threatening events despite passive delivery of oxygen or whose fatigue leads to hypercarbia require intubation, paralysis, and ventilation. Subsequent management is complex, with frequent need to suction the airway and intervene when bradycardia or secondary pulmonary processes occur. Mist by tent can be useful in some infants with thick, tenacious secretions and excessively irritable airways. 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 for 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. Largevolume feedings are avoided. Within hr, the direction and severity of disease usually are obvious by analysis of recorded information. Many infants have marked improvement upon hospitalization and antibiotic therapy, especially if they are early in the course of disease or have been removed from aggravating environmental smoke, excessive stimulation,

10 or a dry or polluting heat source. Hospital discharge is appropriate if over a 48-hr period disease severity is unchanged or diminished, no intervention is 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 those with complicated disease. Portable oxygen, monitoring, or suction apparatus should not be needed at home. Antibiotics. An antimicrobial agent is always given when pertussis is suspected or confirmed primarily to limit the spread of infection and secondarily for possible clinical benefit. Macrolides are preferred agents, which have similar efficacy in vitro ( Table ). Resistance has been reported rarely. A 7- to 10-fold relative risk for infantile hypertrophic pyloric stenosis (IHPS) has been reported in neonates treated with orally administered erythromycin. Azithromycin is the preferred agent for use in neonates. Limited use in neonates has not signaled increased risk for IHPS. All infants <1 mo of age treated with any macrolide should be monitored for symptoms of pyloric stenosis.

11 Recommended Antimicrobial Treatment and Postexposure Prophylaxis for Pertussis, by Age Group PRIMARY AGENTS ALTERNATE AGENT[*] AGE GROUP Azithromycin Erythromycin Clarithromycin TMP-SMZ <1 mo Recommended Not preferred. Not Contraindicated for infants agent. 10 mg/ Erythromycin is recommended aged <2 mo (risk for kg/day in a associated with (safety data kernicterus) single dose for 5 days (only limited safety data available) infantile hypertrophic pyloric stenosis. unavailable) Use if azithromycin is unavailable; mg/kg/ day in 4 divided doses for 14 days. 1 5 mo 10 mg/kg/day mg/kg/ 15 mg/kg/day Contraindicated at age <2 mo in a single dose day in 4 divided in 2 divided For infants aged 2 mo. for 5 days doses for 14 days. doses for 7 days TMP 8 mg/kg/day, SMZ 40 mg/kg/day in 2 divided doses for 14 days Infants (aged 6 mo) and children 10 mg/kg in a single dose on day 1 then mg/kg/ day (maximum 2 g/day) in 4 15 mg/kg/day in 2 divided doses TMP 8 mg/kg/day, SMZ 40 mg/kg/day in 2 divided doses for 14 days mg/kg/day (maximum 500 mg) on days 2 5 divided doses for 14 days. (maximum 1 g/ day) for 7 days Adults 500 mg in a single dose on day 1 then 250 mg/day on days g/day in 4 divided doses for 14 days. 1 g/day in 2 divided doses for 7 days TMP 320 mg/day, SMZ 1,600 mg/day in 2 divided doses for 14 days From Centers for Disease Control and Prevention: Recommended antimicrobial agents for treatment and postexposure prophylaxis of pertussis CDC Guidelines. MMWR 2005;54:1 16. * Trimethoprim-sulfamethoxazole (TMP-SMZ) can be used as an alternative agent to macrolides in patients aged 2 mo who are allergic to macrolides, who cannot tolerate macrolides, or who are infected with a rare macrolide-resistant strain of Bordetella pertussis.

12 Adjunct Therapies. No rigorous clinical trial has demonstrated a beneficial effect of β2- adrenergic stimulants such as salbutamol or 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. Isolation. Patients with suspected pertussis are placed in respiratory isolation with use of masks by all health care personnel entering the room. Screening for cough should be performed upon entrance of patients to emergency departments, offices, and clinics to begin isolation immediately and until 5 days after initiation of macrolide therapy. Children and staff with pertussis in child-care facilities or schools should be excluded until macrolide prophylaxis has been taken for 5 days. Care of Household and Other Close Contacts. A macrolide agent 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 ( Table ). The same age-related drugs and doses for prophylaxis are used for treatment. Visitation and movement of coughing family members in the hospital must be assiduously controlled until erythromycin has been taken for 5 days. Close contacts <7 yr of age who have received fewer than 4 doses of pertussis-containing vaccines should have vaccination initiated or continued to complete the recommended series. Children <7 yr of age who received a 3rd dose >6 mo before exposure or a 4th dose 3 yr before exposure should receive a booster dose. Individuals 9 yr should be given a Tdap (adolescent/adult formulation of tetanus and diphtheria toxoids and acellular pertussis) booster if they have not previously received Tdap and >2 yr have passed since receipt of a diphtheria-containing vaccine. Coughing

13 health care workers, with or without known exposure to pertussis, should be promptly evaluated for pertussis (see Chapter 171 ). COMPLICATIONS. Infants <6 mo of age have excessive mortality and morbidity, with infants <2 mo of age having the highest reported rates of pertussisassociated hospitalization (82%), pneumonia (25%), seizures (4%), encephalopathy (1%), and death (1%). Infants <4 mo of age account for 90% of cases of fatal pertussis. Preterm birth and young maternal age are significantly associated with fatal pertussis. The principal complications of pertussis are apnea, secondary infections (such as otitis media and pneumonia), and physical sequelae of forceful coughing. The need for intensive care and artificial ventilation is usually limited to infants <3 mo of age. Respiratory failure due to apnea or secondary bacterial pneumonia are events precipitating intubation and ventilation. Progressive pulmonary hypertension or hemorrhage (especially in very young infants) and secondary bacterial pneumonia are usual causes of death. 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. Bronchiectasis has been reported rarely after pertussis. Children who have pertussis before the age of 2 yr may have abnormal pulmonary function into adulthood. Increased intrathoracic and intra-abdominal pressure during coughing can result in conjunctival and scleral hemorrhages, petechiae on the upper body, epistaxis, hemorrhage in the central nervous system (CNS) and retina, pneumothorax and subcutaneous emphysema, and umbilical and inguinal hernias. Laceration of the lingual frenulum is not uncommon. CNS abnormalities occur at a relatively high frequency and are almost always a 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. Lack of associated respiratory signs in some young infants with apnea raises the possibility of a primary effect of PT on the CNS. Seizures are usually a result of hypoxemia, but hyponatremia from excessive secretion of antidiuretic hormone during pneumonia can occur. The only neuropathology

14 documented in humans is parenchymal hemorrhage and ischemic necrosis. Particular association of pulmonary hypertension with pertussis is unexplained. Despite extracorporeal membrane oxygenation, this complication portends a mortality rate of >80%. PREVENTION. Universal immunization of children with pertussis vaccine, beginning in infancy with periodic reinforcing doses, is central to the control of pertussis (see Chapter 170 ). There is no serologic correlate of protection. Three diphtheria and tetanus toxoids combined with acellular pertussis (DTaP) vaccines currently are licensed in the USA for children <7 yr of age. DTaP vaccines have fewer adverse effects than the vaccines containing whole-cell pertussis (DTP), which continues to be given to infants and children in many other countries. Acellular pertussis vaccines all contain inactivated PT and contain 2 or more other bacterial components (FHA, Pn, and Fim 2 and 3). Clinical efficacy against severe pertussis, defined as paroxysmal cough >21 days, is 80 85%. Mild local and systemic adverse events as well as more serious events (including high fever, persistent crying of 3 hr duration, hypotonic hyporesponsive episodes, and seizures) occur significantly less frequently among infants who receive DTaP compared with DTP vaccine. DTaP-containing vaccines can be administered simultaneously with any other vaccines used in standard schedules for children. Three (primary) doses of DTaP should be administered during the 1st year of life, generally at ages 2, 4, and 6 mo of age. A 4th dose (1st booster) is recommended for children at mo of age, at least 6 mo after the 3rd dose, to maintain adequate immunity during the preschool years. The 4th dose may be administered as early as 12 mo of age, provided 6 mo have elapsed since the 3rd dose and the child is unlikely to return at mo of age. The 5th dose (2nd booster) is recommended for children at 4 6 yr of age to confer continued protection against disease during the early years of schooling. A 5th dose is not necessary if the 4th dose in the series is administered on or after the 4th birthday. Pertussis-containing vaccines and combination vaccines should be used only in the dosing series and age group for which each is licensed, and when all components are indicated. When feasible, the same DTaP product is recommended for the 1st 3 doses of the

15 vaccination series. Local reactions increase in rate and severity with successive doses of DTaP, although never reaching the magnitude of reactions following similar doses of DTP. Up to 2% of 4th and 5th doses of DTaP are associated with entire limb swelling, with concurrent pain and erythema in approximately ½ of children affected. Swelling subsides spontaneously without sequelae. Exempting children from pertussis immunization should be considered only in the narrow limits as recommended. Exemptors have been shown to have significantly increased risk for pertussis as well as a role in outbreaks of pertussis among immunized populations. If infection with B. pertussis is proved, the individual should complete the immunization series with at least diph theria and tetanus toxoids; some experts recommend including the pertussis component as well. In 2005, 2 tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine, adsorbed (Tdap) products were licensed for use in older individuals as single-dose booster vaccines to provide protection against tetanus, diphtheria, and pertussis. The preferred age for Tdap vaccination is yr. All adolescents yr of age who received Td, but not Tdap, should receive a single dose of Tdap to provide protection against pertussis if they have completed the recommended childhood DTP/DTaP vaccination series. An interval of at least 5 yr between Td and Tdap is encouraged in routine situations to reduce the risk for local and systemic reactions after Tdap vaccination. However, an interval of <5 yr between Td and Tdap can be used. Both Tdap and tetravalent meningococcal conjugate vaccine should be administered to adolescents yr of age during the same visit if both vaccines are indicated and available. Adults yr of age should receive a single dose of Tdap to replace their next Td booster dose. Priority for Tdap vaccine should be given for health care workers who have contact with children and for eligible family contacts of neonates. An important objective of administering the adolescent pertussis booster is to protect adolescents and adults against pertussis to control endemic and epidemic spread to young infants who have not completed primary immunization and are at high risk for pertussis and its complications.