Version May 2024
INTRODUCTION — Pertussis, also known as "whooping cough," is a highly contagious respiratory illness caused by Bordetella pertussis. A Chinese reference to "the cough of 100 days" by Chao Yuanfang in the early 7th century may have referred to pertussis [1]. In 1679, Sydenham named the illness pertussis, from the Latin term meaning "intense cough." These names describe the key clinical features of pertussis infection. However, the classic clinical manifestations of pertussis infection (paroxysmal cough, inspiratory whoop, and post-tussive emesis) are frequently absent in adolescents and adults.
The microbiology, epidemiology, and pathogenesis of pertussis are reviewed here. The clinical manifestations, diagnosis, management, and prevention of pertussis are discussed separately. (See "Pertussis infection in adolescents and adults: Clinical manifestations and diagnosis" and "Pertussis infection in infants and children: Treatment and prevention" and "Pertussis infection in infants and children: Clinical features and diagnosis".)
MICROBIOLOGY — Pertussis is caused by the gram-negative coccobacillus B. pertussis, a strict human pathogen with no known animal or environmental reservoir [2]. The organism is fastidious, surviving only a few hours in respiratory secretions and thus requiring special media for culture.
Eight additional Bordetella species have been described: B. parapertussishu, B. parapertussisov (ovine-adapted parapertussis), B. bronchiseptica, B. avium, B. hinzii, B. holmesii, B. trematum, and B. petrii [3]. Three of these species (B. parapertussis, B. bronchiseptica, and B. holmesii) can cause respiratory illness in humans. B. parapertussis may cause a spectrum of disease ranging from a nonspecific upper respiratory tract illness to classic pertussis (ie, clinically indistinguishable from that of B. pertussis) [4,5]. B. bronchiseptica causes respiratory infections in a variety of mammals; human infection most often occurs in immunocompromised hosts with animal exposure [6]. Unlike B. pertussis, B. holmesii may also cause bacteremia; asplenia is the most common risk factor, but other immunocompromising conditions have been reported [7-11].
EPIDEMIOLOGY — Pertussis is a highly contagious respiratory illness. In adolescents and adults, infection may result in a protracted cough and is occasionally associated with substantial morbidity. In children, and particularly infants, morbidity is more often substantial, and the disease may be fatal.
Transmission — The incubation period for B. pertussis ranges from 1 to 3 weeks but is most typically 7 to 10 days. This is in contrast with the shorter incubation period (one to three days) for viral upper respiratory infections associated with cough, such as the common cold.
Pertussis infection is spread via respiratory droplets, which are aerosolized by paroxysms of coughing [12]. In one study, approximately one-third of exposed individuals within households developed pertussis [13]. A systematic review of similar studies found that the proportion of household contacts with laboratory evidence of infection who were asymptomatic ranged from 5 to 56 percent, and 3 to 46 percent had a mild respiratory illness (ie, nonclassical symptoms of pertussis) [14]. Thus, asymptomatic infection appears to be common and may contribute to transmission of pertussis between household contacts.
Individuals with pertussis are considered infectious until they have completed five days of appropriate antibiotic treatment [15-17].
Incidence — Prior to the introduction of a whole-cell vaccine in the United States in the late 1940s, pertussis was a devastating illness with a relatively high infant mortality rate. Widespread pertussis vaccination of children led to a dramatic decline in disease incidence, from a peak of more than 250,000 reported cases in 1934 to a nadir of 1010 cases in 1976 (figure 1) [18].
Cyclical epidemics continue to occur every two to five years as they did in the prevaccine era. These epidemics have been superimposed on the steadily rising incidence in the United States and many other developed countries. The unchanged cyclical epidemic pattern of pertussis suggests that the overall circulation of B. pertussis in the population has not been affected by the vaccine [19].
In the prevaccine era, the highest rates of pertussis infection were reported in the spring and summer months, but this seasonal variation declined after vaccine introduction. Along with the ongoing overall increase in pertussis infection, reports suggest recurrent seasonality with the peak occurring in the summer months [20,21].
Since the 1970s, there has been a steady increase in reported cases of pertussis in the United States [22]. In 2010, there were 27,550 reported cases and outbreaks in several states (figure 2) and in 2012, there were more than 48,000 cases [23,24]. Between 2000 and 2016, more than 330,000 cases were reported in the United States [25]. Because pertussis is underreported and underdiagnosed in adults, the actual incidence is likely substantially higher. This was demonstrated by a study including patients ≥18 years old who had not received pertussis vaccination in the last five years; the incidence of pertussis (based on seroepidemiologic studies) was substantially higher than the clinically reported incidence (0.84 versus 699 per 100,000 inhabitants) [26]. A retrospective cohort study was used to develop a machine-learning algorithm to identify undiagnosed or misdiagnosed episodes of pertussis in adolescent and adult patients. Compared to data from the Centers for Disease Control, the inclusion of cases of pertussis identified by the algorithm increased the estimated incidence in all the years studied. This was most dramatic in adolescents (who consistently had the highest rates), for whom the incidence was 110-fold higher. This highlights the extent of potential underreporting of the disease [27,28].
The cause for the rising incidence of pertussis is not fully understood. Possible explanations include increased clinician awareness, increased public health reporting, increased availability of more sensitive diagnostic tests (particularly polymerase chain reaction [PCR]), waning vaccine-induced immunity in adolescent populations (as immunity following vaccination or infection is not lifelong) [29], decreased use of pertussis vaccine, genetic changes in the circulating strains of pertussis, and a true increase in circulating B. pertussis. Widespread use of PCR testing has improved clinicians' ability to confirm the diagnosis [30,31]. Numerous reports indicate that waning immunity with the acellular pertussis vaccines (DTaP and Tdap) is playing a major role in the increased incidence [25].
Since 1997, acellular pertussis vaccine (DtaP) has been recommended for all five childhood doses (the last of which should be administered between ages four and six years). Prior to 1997, vaccination was with whole-cell pertussis vaccine (DTwP) [32]. The DTwP vaccine was effective in preventing childhood pertussis, although immunity gradually waned 5 to 10 years after completing the childhood series, resulting in risk for infection in adolescence and adulthood [33,34]. Because the incidence of local reactions (pain, redness, swelling) and systemic reactions (fever, anorexia) with DTwP was relatively high [35], acellular pertussis vaccines (DtaP) were introduced for childhood vaccination in the United States in the early 1990s. Clinical trial data suggest DtaP has similar efficacy to DTwP, with a lower incidence of adverse effects [32,36]; however, the currently available DtaP formulations offer less short-term protection than DTwP [37].
Since 2005, an increased risk of pertussis has been observed in the first cohort of children who received the DtaP series as they reach 7 to 10 years of age [38]. Similarly, several reports suggest that the immunity following administration of the fifth DtaP dose wanes more rapidly than expected [39-42], leaving a gap in immunity between the last childhood dose of DtaP and the Tdap booster vaccine (which is suggested to be administered at 11 to 12 years of age) [43]. Adolescents who received the DtaP vaccine in childhood appear to have a substantially higher risk of contracting pertussis than those who received the DTwP vaccine [44,45] and the duration of Tdap vaccine protection is less in adolescents who received Dtap in childhood (rather than DTwP) [46].
Worldwide, 90 percent of the 30 to 50 million annual cases of pertussis occur in resource-limited countries. About 300,000 cases result in death [47], with mortality occurring predominantly in infants (who are too young to have received vaccination) and unvaccinated or undervaccinated children.
Evolving epidemiology — In the United States, a substantial portion of the increasing incidence in reported pertussis cases since 1990 is attributable to increased rates of infection in adolescents and adults [48-51]. In the prevaccine era, more than 90 percent of reported cases of pertussis occurred in children <10 years old [49]. In the late 1990s, about one-half of reported cases occurred in adolescents and adults [18]; similar rates are observed in data from 2000 to 2016 [25]. The incidence of reported pertussis cases among infants has steadily increased since 1980 [25,52,53].
B. pertussis infection in adolescents and adults appears to be much more common than many clinicians appreciate [30,54]. This may be because the manifestations of pertussis are often less severe than in infants and children. Studies of adolescents and adults with cough illnesses lasting ≥1 week in nonoutbreak settings indicate that pertussis is responsible for 13 to 20 percent of cases; the overwhelming majority of these patients actually had a substantially longer duration of illness (>3 weeks) [30,55]. The incidence of pertussis is quite low in adults with cough duration ≤4 weeks [56] (see "Pertussis infection in adolescents and adults: Clinical manifestations and diagnosis", section on 'Adolescents and adults'). A seroprevalence study of adults (age 20 to 39 years) in 14 European countries showed rates of infection ranging from 0.2 to 5.7 percent and rates of infection within the past few years as high as 13.9 percent across the countries [57].
Adolescents and adults with unrecognized pertussis serve as a reservoir of infection for infants and children [58]. In the United States, one-half of infants with pertussis infection require hospitalization and nearly 90 percent of pertussis deaths occur in infants [25]. Epidemiologic studies have shown that most infants acquire the infection from adolescents and adults in their own household [59-63]. Siblings of infants have been identified as the most common identifiable source of transmission in one study [64], likely reflecting increased susceptibility to infection of children and adolescents who received the acellular pertussis vaccine.
Primate data suggest that the acellular pertussis vaccine may protect individuals from clinical disease, but asymptomatic or subclinical infection may still develop and result in spread to susceptible individuals [65]. Mathematical modeling suggests that this may be an important reason for the increase in incidence in the United States and United Kingdom [66]. Despite the introduction of acellular pertussis vaccines over 20 years ago the incidence of pertussis has been increasing in most parts of the world over the past decade, with a shift in cases from young children to fully vaccinated adolescents and adults, mainly driven by waning vaccine immunity [67,68].
An important misconception is that childhood pertussis vaccination or prior infection confers lifelong immunity. Because protective immunity wanes, booster vaccination is recommended for adolescents (preferably at age 11 or 12), adults, and for women with each pregnancy. An economic model found that increased vaccination coverage for among United States adults aged ≥50 years would be favorable [69].
Rates of vaccination with Tdap among adults in the United States, while improving slightly in recent years, are still under 25 percent [70]. Similarly, a seroepidemiology study in Hungary found that 85 percent of adults were seronegative for pertussis and therefore susceptible to infection [71]. (See "Pertussis infection in adolescents and adults: Treatment and prevention".)
Risk factors for infection and severe disease — Groups at highest risk of pertussis-related morbidity and mortality include infants (especially those younger than six months), young children who have not been fully immunized, and older adults (ie, aged >65 years). In one study of patients with pertussis in the United States, adults >65 years were frequently hospitalized (14.8 percent) and accounted for 4.8 percent of all pertussis-related deaths [25]. Among adults and adolescents hospitalized with pertussis, high rates of comorbid asthma and, in older adults, chronic obstructive pulmonary disease have been observed [72]. In a pneumonia surveillance study of >19,000 patients in South Africa, B. pertussis was detected in 1.2 percent of patients.
Obesity and pre-existing asthma have been associated with a higher likelihood of developing pertussis [73]. In one study of older teenagers and adults, household contact with a younger teenager increased the risk of pertussis, whereas professional contact with children <1 year of age decreased the risk [74].
Although the cause is uncertain, an excess in the female incidence rate for pertussis infection across all age ranges and various time periods has been observed in several countries [75].
PATHOGENESIS — B. pertussis is transmitted via aerosolized respiratory droplets. It produces a number of biologically active substances and virulence factors that promote cellular attachment, cause local tissue damage or systemic manifestations, and interfere with host defense mechanisms (table 1). After inhalation, the organism adheres to ciliated respiratory epithelial cells of the upper respiratory tract and nasopharynx. A variety of protein adhesins have been implicated in the attachment process; these demonstrate a substantial degree of redundancy [3]. Once attached, they induce local tissue damage via tracheal cytotoxin, dermonecrotic toxin, or adenylate cyclase; this destructive process, with loss of the protective respiratory cells, is likely responsible for microaspiration and therefore for the cough.
Histopathological analysis, using a novel immunohistochemical technique, of tissue samples obtained from cases of fatal pertussis infection in infants revealed intracellular organisms in alveolar macrophages as well as the ciliated respiratory epithelial cells [76]. This may explain the prolonged duration of cough. The most notable systemic laboratory manifestation is lymphocytosis, which is caused by pertussis toxin (PT). PT may also cause hyperinsulinemia with resultant hypoglycemia in young infants [77,78].
Following infection, antibodies to a variety of antigens develop, including PT, filamentous hemagglutinin, pertactin, fimbriae 2/3, lipopolysaccharide, and adenylate cyclase. Many of these antigens form the components of pertussis vaccines. Pertactin, a virulence factor that is thought to promote adherence of B. pertussis to the upper respiratory epithelium, is a pertussis acellular vaccine immunogen. A screening study of 1300 surveillance and outbreak isolates in the United States demonstrated a dramatic increase in pertactin-deficient B. pertussis isolates [79]. In addition, an association has been observed between prior (acellular) vaccination and infection with pertactin-deficient B. pertussis, suggesting that previously vaccinated individuals are more susceptible to this strain [80].
SUMMARY
●Microbiology – Bordetella pertussis is a fastidious gram-negative coccobacillus that requires special media for culture. It is exclusively a human pathogen. (See 'Microbiology' above.)
●Epidemiology
•The introduction of the whole-cell pertussis vaccine in the United States in the late 1940s led to a dramatic decline in disease incidence; however, the number of reported cases in the United States and many other countries has been steadily rising since the 1970s. The newer acellular pertussis vaccines appear to be less efficacious than the whole-cell vaccines used previously. (See 'Incidence' above.)
•Adolescents and adults with unrecognized pertussis represent a reservoir of infection for infants and children, in whom infection is associated with substantially higher morbidity and mortality. This has implications for vaccine recommendations in adolescents and adults. (See 'Evolving epidemiology' above and "Pertussis infection in adolescents and adults: Treatment and prevention", section on 'Vaccination'.)
●Transmission and pathogenesis
•The incubation period for B. pertussis is typically one week but may be three weeks or longer. (See 'Transmission' above.)
•B. pertussis is highly contagious and is transmitted via aerosolized respiratory droplets. After inhalation, the organism adheres to ciliated respiratory epithelial cells of the upper respiratory tract and nasopharynx, causing local tissue damage. (See 'Pathogenesis' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Dr. Christopher Ohl, who contributed to an earlier version of this topic review.
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