Pertussis, or whooping cough, is a highly contagious respiratory tract infection caused by the bacterium Bordetella pertussis. It is characterized by severe coughing spasms often associated with vomiting and is sometimes referred to as the “100-day cough.”¹ The burden of pertussis disease is substantial. Infants suffer the greatest complications, which include pneumonia, encephalopathy, nutritional problems, and, in rare cases, death.^2–5 Adolescents and adults infected with pertussis experience sleep disturbances, work loss, restrictions on activities, and substantial direct and indirect costs.^6–12

Like many serious diseases, pertussis is preventable by routine childhood immunization. Following the widespread use of whole-cell pertussis vaccines containing diphtheria and tetanus toxoids in the 1940s, the mean incidence rates of pertussis decreased from 150/100,000 to ∼1/100,000 by 1980.^13–15 However, this decline was not sustained. Since the 1980s, the number of reported pertussis cases has gradually increased in all age groups despite stable or increasing vaccination rates; the greatest increase has been in adolescents and young adults. In 1996, less-reactogenic diphtheria, tetanus, and acellular pertussis vaccines were licensed and recommended for routine use in infants and young children, replacing whole-cell pertussis and diphtheria and tetanus toxoid vaccines completely in the United States.^16,17 During the 1990s the incidence of pertussis remained stable among infants 5–11 months of age.¹⁸ However, pertussis outbreaks among adolescents increased,^15,19–21 probably because of waning immunity against pertussis.³

In this article, an overview of pertussis will be provided, focusing on epidemiology, sources of infection, and trends in incidence patterns, particularly related to the steady increase seen in adolescents. Issues surrounding long-term protection after infant vaccination will also be discussed.

EPIDEMIOLOGY OF PERTUSSIS

In 2003, a total of 11,647 pertussis cases were reported to the Centers for Disease Control and Prevention, representing the highest incidence of pertussis since 1964 (Fig. 1). ^22,23 Pertussis incidence particularly increased among adolescents as shown in Figure 2, and pertussis cases among infants too young to have received three doses of diphtheria-tetanus-pertussis vaccine also increased.¹⁸

There has always been concern about underreporting of pertussis cases. Routinely, cases of pertussis with demographic and clinical information are reported by state health departments to the Centers for Disease Control and Prevention through the National Electronic Telecommunications System for Surveillance and the Supplemental Pertussis Surveillance System. The latter collects more detailed information about cases, including clinical characteristics and vaccination history. To estimate the degree of underreporting, both systems were compared using capture-recapture methods (Table 1). ^24,25 These studies suggested that there was a significant amount of underreporting with likely 5–6 times more cases than reported. Of concern, underreporting of pertussis cases may be even higher for adolescents and adults than for young children, because symptoms may be more atypical in the adolescent group.

In addition, there is considerable variation in the incidence of pertussis and the proportion of cases in adolescents and adults among various states.^19,26 The state of Massachusetts pertussis laboratory has provided serologic assays to measure coughing illnesses in adolescents and to investigate outbreaks of pertussis in middle schools and high schools. Rates of pertussis in adolescents in this state are among the highest in the nation but may simply reflect excellent surveillance capabilities. Similar findings were reported from a statewide outbreak in Vermont in 1996 where aggressive case finding identified a large number of cases.¹⁹

SOURCES OF INFECTION FOR INFANTS

Infants and young children who are not immunized or not fully immunized are at highest risk for developing severe pertussis and serious life-threatening complications. They are also significantly more likely to be hospitalized for pertussis.¹⁸ As shown in Table 2, from 1997 to 2000, the proportion of patients hospitalized or developing complications of pertussis was highest among infants younger than 6 months and decreased with age.²⁷ Currently, low levels of antibody to pertussis antigens are present in maternal sera, although when antibody is available, it is effectively transferred through the placenta.^28,29

A number of studies have evaluated the role of adolescents as the source of transmission of pertussis to infants.^30–32 An epidemiologic study published in 2004 examined reported pertussis cases in four states (Georgia, Illinois, Minnesota, and Massachusetts) to determine the source of pertussis infection among infants.³⁰ Results demonstrated that among the 264 case-infants, mothers were the source for 84 (32%) of the cases, and another family member was the source for 113 (43%) of the cases, thus concluding that family members were the main sources of pertussis.

In 1990, Long et al³² evaluated the transmission of pertussis among 4 infants admitted to the hospital and their 18 family members. Results of their study indicated that although only 20% of the family members had culture-confirmed pertussis, 83% were found to have serologic evidence of infection with at least 1 symptomatic adult per family. Therefore, index pertussis cases among infants are often secondary to primary infections in other older family members. Similarly, in another study, Deen et al³³ evaluated household contacts of primary pertussis cases to determine clinical and laboratory evidence of infection. In 39 households, 255 subjects were identified to have household exposure to pertussis, and 53% of the primary sources of infection in these infants were from individual family members older than 13 years of age, emphasizing the role of adolescents and young adults in disease transmission to infants.

Finally, in a study focusing on the epidemiologic features of 1,082 children hospitalized with pertussis in Canada from 1991 to 1997, 92% of the cases were in children younger than 1 year of age, and 79% of the cases were in children younger than 6 months of age.³¹ A total of 10 deaths were reported; 6 in children younger than 1 month of age. The source of contagion for the hospitalized infants was identified in 40% of the cases, with 53% of these attributed to exposure from a sibling and 20% from a parent.

SOURCES OF INFECTION FOR ADOLESCENTS

School outbreaks clearly demonstrate the role of other adolescents in the transmission of pertussis. In a schoolwide pertussis outbreak in Yavapai County, AZ, from September 2002 to February 2003, 485 cases of pertussis were identified, with the highest attack rate among eighth graders.³⁴ The median age of persons with pertussis in this outbreak was 13 years, and transmission between schoolmates was clearly shown. Similar outbreaks with comparable patterns have been documented in Massachusetts,³⁵ thus emphasizing the role of adolescents in transmission of pertussis to others.

LONG-TERM PROTECTION AFTER INFANT VACCINATION

The reasons for increases in pertussis incidence are multiple. Improvements in the diagnosis and reporting of pertussis cases have likely played a role.^15,27,36 In addition, it has been shown previously that vaccine-induced immunity to pertussis wanes 5–10 years after vaccination with whole-cell pertussis vaccines.^26,37 During an outbreak of pertussis in a Michigan community it was determined that the population most susceptible were individuals for whom ≥12 years had elapsed since a whole-cell pertussis vaccination. The attack rate was ∼95% in these individuals,²⁶ whereas those recently vaccinated had much lower attack rates (Table 3). In another similar study assessing the efficacy of pertussis vaccine 1–7 years after immunization, significant waning of immunity was noted 4 years after vaccination.³⁷

A seroepidemiologic study conducted in Nashville in 1996 also demonstrated evidence of waning immunity over time. Antibody titers to pertussis toxin and filamentous hemagglutinin were measured in 585 serum samples collected from healthy individuals 1–65 years old in Nashville, TN.³⁸ Increases in antibody titers to both antigens were seen in individuals 4–6 years of age, corresponding to the 5th dose of diphtheria, tetanus, and acellular pertussis vaccine given at that time. However, the antibody titers rapidly declined. Then at 13–16 years of age, the pertussis toxin and filamentous hemagglutinin antibody titers increased, reflecting boosting of antibody by natural acquisition of pertussis infection during these adolescent years (Fig. 3). After 30 years of age, the antibody titers leveled off and began to decrease again. These data suggest that after the last vaccination at 4–6 years of age, increases in antibody titers during the adolescent years reflect exposure to natural B. pertussis.

Although acellular pertussis vaccines appear to provide longer-lasting cellular than humoral immune responses,³⁹ waning immunity after vaccination with acellular pertussis vaccines likely occurs. Booster vaccinations for pertussis have been proven to be safe and effective in studies recently sponsored by the National Institutes of Health.⁴⁰ This prospective, randomized, double-blind trial involving 2,784 adolescents and adults aged 15–65 years⁴⁰ showed that the acellular pertussis vaccine was effective in preventing confirmed pertussis infections and was not associated with serious vaccine-related adverse events.

CONCLUSIONS

Although pertussis is a vaccine-preventable disease, it continues to be a major cause of morbidity and mortality in the United States, especially among the young. Furthermore, the complications of pertussis are troublesome and can be fatal. Acellular pertussis vaccines have proven to be safe and effective and are recommended for routine administration in infants and young children. Widespread immunization with pertussis vaccine has helped control the incidence of disease among children and has helped reduce pertussis-related morbidity, but waning immunity and increases in adolescent pertussis disease have been reported. Many patients infected with B. pertussis are adolescents who, seemingly as the result of waning immunity, represent the population most likely to spread the infection to others, particularly susceptible infants. Methods to detect pertussis still need improvement, and, despite existing surveillance systems, significant underreporting of pertussis exists among adolescents and adults. However, in spite of the limitations to the pertussis surveillance system, there is adequate justification that vaccination of adolescents with acellular pertussis booster vaccines would reduce disease in this population and likely in young infants as well.