Old Disease, Innovative Response

Commentary

Disease caused by Bordetella pertussis was once a major cause of morbidity and mortality among infants and young children in industrialized countries.¹ Prior to widespread vaccination of infants and toddlers, there were approximately 250 000 cases of pertussis each year in the United States among all age groups. Serious complications such as bronchopneumonia, encephalopathy, and death complicated the course of one-quarter of affected infants younger than 6 months of age.² In the early 20th century, pertussis killed more than 5 of every 1000 children born in the United States, making this disease an important early target for immunization efforts.¹

Although the incidence of pertussis declined after universal pertussis vaccination of infants and toddlers began, the disease remains common. In 2006, more than 15 000 cases were reported³ ; the actual number of cases is thought to be greater because pertussis frequently goes undiagnosed in adolescents and adults.⁴ Pertussis results in considerable morbidity among adults and adolescents, whose immunity from childhood vaccination has likely waned. On average, affected adults miss 10 days of work and incur nearly $800 in direct and indirect costs, and affected adolescents miss 6 days of school.⁵

The consequences among infected infants are far more severe: two-thirds of infants with pertussis require hospitalization,⁶ and more than 85% of pertussis-associated deaths occur among infants younger than 6 months.⁷ More worrisome is that the incidence of pertussis continues to increase among infants who are too young to be directly protected by vaccination.⁷ Importantly, the source case for infected infants is typically a close family member, such as a parent or grandparent.⁶

One of the most promising strategies for protecting high-risk infants from pertussis is to boost immunity against pertussis among adolescents and adults, using the tetanus-diphtheria-acellular pertussis vaccine (Tdap) that has been recommended for individuals aged 11 to 64 years since 2005.⁸ A study of parents in the immediate postpartum period in 1 center illustrated that it was possible to administer Tdap to more than 80% of parents of children in the neonatal intensive care setting.⁹ Whether this level of vaccination success can be replicated in other clinical populations remains to be seen.

What other approaches can further reduce the burden of pertussis among infants? One strategy receiving attention is an accelerated immunization schedule in infancy. Two to 3 doses of pertussis toxoid–containing vaccine are required for effective protection. According to the standard immunization schedule, doses of the diphtheria, tetanus toxoid, and acellular pertussis vaccine (DTaP) are administered at 2, 4, and 6 months of age with a minimum 8-week interval between doses.¹⁰ Other vaccines including the inactivated polio vaccine and the heptavalent pneumococcal conjugate vaccine are administered concurrently with DTaP. An alternative schedule, which reduces the minimum interval between doses from 8 weeks to 4 weeks, allows children with delays in immunization to complete recommended immunizations in a timely manner.

In an article in the May issue of the Archives of Pediatrics & Adolescent Medicine, a theme issue on innovations in vaccine delivery, Bronson-Lowe and Anderson¹¹ explore another potential role for the 4-week minimum interval schedule for pertussis vaccination. During a community outbreak of hundreds of cases of pertussis in Arizona, the minimum interval schedule was recommended for all infants who had not yet received the first 3 DTaP doses. The authors, using data from a state immunization registry, identified 2 cohorts of infants eligible to receive DTaP vaccination; the first group received their initial DTaP dose during the Arizona outbreak and the second group received their initial DTaP dose 1 year before the outbreak. Approximately 90 000 infants were included in the study. Infants in the outbreak and nonoutbreak cohorts were further categorized as receiving either the standard vaccination schedule or the minimum interval vaccination schedule, depending on when each dose of DTaP was administered. Infants receiving DTaP on the minimum interval schedule during the outbreak period were more likely than infants vaccinated on the standard schedule to receive all 3 doses of DTaP, inactivated polio vaccine, and heptavalent pneumococcal conjugate vaccine. The improvements in overall vaccination rates were also present during the nonoutbreak period, although the magnitude of improvement was less during this nonepidemic period.¹¹

This finding is important because advisory bodies have not traditionally recommended use of a minimal interval or accelerated schedule of vaccination for infants during pertussis outbreaks because it would not match the schedule of other recommended vaccinations. In the worst-case scenario, the number of cases of other vaccine-preventable diseases would also increase, compounding the medical consequences of the original pertussis outbreak. There is, however, a physiological basis to support the use of an accelerated schedule as vaccination at 1 month of age produces similar antibody responses to vaccination at 2 months of age.¹² Furthermore, receipt of 3 doses of pertussis vaccine at 4-week intervals provides a high degree of clinical protection against pertussis.¹³ While many important questions remain regarding optimal use of immunizations in the context of community-wide epidemics, Bronson-Lowe and Anderson provide critical support for the use of a minimum interval schedule for DTaP during community pertussis outbreaks.

Another important aspect of the findings from this study is how many clinicians must have followed the state health department's interim recommendation to accelerate DTaP immunization for infants during the pertussis outbreak. Urgent changes in childhood immunization recommendations—for example, during recent vaccine-supply shortages—have not always fared so well.¹⁴ What may have facilitated an effective response by clinicians in the Arizona situation is that the recommendations were issued by the state health department, which is often seen by local clinicians as the most authoritative source in times of vaccine-remediable crises.¹⁵ Another factor predisposing to success may have been clinicians' and parents' great familiarity with the DTaP vaccine.

Vaccines remain an extraordinarily effective and cost-effective means of preventing disease for children and adults. The study by Bronson-Lowe and Anderson,¹¹ and other articles in the May issue of the Archives of Pediatrics & Adolescent Medicine, are reminders that there are innovative ways to promote immunization and administer vaccines that offer the opportunity to obtain additional benefits from these familiar tools.