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Continued pertussis outbreaks call vaccine effectiveness into question
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Immunization strategies to control pertussis infection and disease in infants and children have been in use for more than 70 years, yet large outbreaks and epidemics, including deaths, have recently occurred. The current acellular pertussis vaccine, DTaP, has been recommended in the pediatric immunization schedule for nearly 20 years. This acellular vaccine replaced the whole-cell vaccine, which had been used since approximately 1950. With recent epidemics of pertussis occurring, the efficacy of the acellular vaccines and current pertussis immunization strategies have come into question.
Evolving vaccines
The older whole-cell pertussis vaccines were composed of whole Bordetella pertussis bacterial organisms, and although they were antigenic and effective, they also were reactogenic, which prompted pharmaceutical manufacturers to develop more purified, and less reactogenic, vaccine products. Acellular vaccines, containing specified antigenic components of B. pertussis, were recommended in the pediatric immunization schedule in 1997. DTaP vaccines currently available differ in B. pertussis antigenic components, containing up to five antigenic components. Animal studies suggest that T-cell immune responses differ between the diphtheria, tetanus toxoids and whole-cell pertussis vaccine (DTwP) and DTaP, and this may contribute to differences in clinical efficacy between them.
Recent large epidemics of pertussis in the United States have heightened concern over the control of pertussis and the efficacy of current strategies, including the specific acellular vaccines used for the primary immunization series and booster vaccines, Tdap, given to adolescents and adults. Before the large-scale utilization of any pertussis vaccine, pertussis disease was widespread in the U.S. — 157 cases per 100,000 population, with 1.5 deaths per 1,000 infants. It is known that the incidence of pertussis is cyclical, with peaks occurring every 3 to 5 years. Infants aged younger than 12 months have the greatest risk for hospitalization and death.
While pertussis disease has decreased significantly since implementation of primary immunization strategies, reported cases have been increasing since the early 1980s. Recent epidemics have occurred, notably in California in 2010 and 2014, and in Washington (approximately 5,000 cases) and Wisconsin (more than 6,000 cases) in 2012. More than 9,000 cases were reported in 2010 in California, including 808 hospitalizations and 10 infant deaths (incidence rate of 24.6 cases per 100,000 population). Four years later, nearly 9,935 cases were reported (incidence rate of 26 cases per 100,000 population) in the state.
Recent evaluation of pertussis vaccine efficacy
Several studies have assessed the effectiveness of pertussis control with use of DTaP vaccines and DTwP vaccines. Klein and colleagues used a case-control design to evaluate pertussis control in children receiving primary pertussis vaccination from whole-cell and acellular vaccines. Patients aged 10 to 17 years in northern California diagnosed with pertussis via PCR testing (n = 138) were compared with PCR-negative (n = 899) and matched controls (n = 54,339). Risk for pertussis by the type of vaccine administered (acellular, whole-cell, or mixed use) was evaluated. Patients who received only whole-cell vaccines were more than fivefold less likely to be diagnosed with pertussis than subjects receiving only acellular vaccines or more than threefold less likely than patients receiving mixed whole-cell and acellular vaccines. The decreasing number of whole-cell pertussis vaccine doses was significantly associated with increased pertussis risk.
In a separate study, Klein and colleagues evaluated the risk for pertussis in patients in northern California relative to the time since receipt of the fifth DTaP (acellular) dose from 2006 to 2011, using a case-control design. Only children receiving acellular pertussis vaccines were studied. Children who were PCR-positive for pertussis (n = 277) were compared with PCR-negative controls (n = 3,318) and matched controls (n = 6,086). PCR-positive children were more likely to have received the fifth DTaP dose earlier than either PCR-negative controls or matched controls, such that the odds of contracting pertussis disease increased by 42% per year.
Additional studies have evaluated Tdap vaccine efficacy in adolescents from recent pertussis epidemics. Klein and colleagues assessed Tdap vaccine efficacy among adolescents aged older than 10 years in northern California who had received DTaP immunization. Vaccine efficacy since receipt of Tdap was estimated by comparison to unvaccinated adolescents. Patients who were PCR-positive for pertussis (n = 1,207) were analyzed, with vaccine effectiveness decreasing from almost 70% from year 1 since receipt to almost 9% by at least 4 years since Tdap receipt.
A study by Koepke and colleagues of Tdap vaccine effectiveness in adolescents in a Wisconsin 2012 pertussis epidemic found similar results of waning Tdap effectiveness, decreasing from about 75% within the first year of receipt to about 12% within 3 to 4 years of receipt. Acosta and colleagues evaluated Tdap vaccine efficacy among adolescents in Washington during its 2012 pertussis epidemic using a case-control design. Among adolescents who received DTaP as the primary vaccination series and were positive for pertussis (n = 450, with 1,246 controls), Tdap vaccine efficacy decreased from 73% within 1 year of receipt to 34% within 2 to 4 years of receipt.
Movement toward revised recommendations
Recent changes in the recommended immunization strategies for children have attempted to improve pertussis control. In 2006 a single dose of Tdap was recommended for adolescents aged 11 to 12 years, and in 2011 a single dose was recommended for pregnant women who had not previously received Tdap. In 2012, this recommendation was expanded to administer Tdap to pregnant women with each pregnancy, with optimal dosing during weeks 27 to 36 of gestation. Unfortunately, uptake of these recommendations has not been strong.
Estimates by the CDC for 2014 indicate only 21.5% of adults aged 19 to 64 years have received Tdap (32.5% for those living with an infant aged younger than 12 months). Recent estimates of Tdap utilization during pregnancy indicate that 14% to 23% of women have received Tdap. Tdap administration during pregnancy provides maternal transfer of protective antibodies to the infant and is believed to be an effective strategy to control pertussis infection in infants aged younger than 2 months who represent the highest-risk group. As the first dose of the DTaP primary immunization series is recommended at age 2 months, protection from active immunization then begins to occur.
Commentaries on the changing epidemiology of pertussis by infectious disease and public health experts have discussed the many factors responsible for increases in reported pertussis cases. These include increased awareness, improved diagnostic techniques (eg, use of PCR), waning immunity from DTaP vaccines and underutilization of current immunization strategies. Many have argued that improved pertussis vaccines are needed.
James D. Cherry, MD, MSc, from the department of pediatrics at the David Geffen School of Medicine at the University of California at Los Angeles, a noted expert on the epidemiology of pertussis, has frequently commented on our current immunization strategies and vaccine products, including potential improvements to vaccines. Cherry and others have written that until we have improved vaccine products and improved immunization schedules, administration of Tdap to every woman who is pregnant should be an immediate priority, to protect the very young infants at most risk from pertussis morbidity and mortality.
The assistance and review of this column by James D. Cherry, MD, MSc, is greatly appreciated.
- References:
- Acosta AM, et al. Pediatrics. 2015;doi:10.1542/peds.2014-3358.
- Cherry JD. Expert Rev Vaccines. 2014;doi:10.1586/14760584.2014.935765.
- Cherry JD. Pediatrics. 2015;doi:10.1542/peds.2014-4118.
- Klein NP, et al. N Engl J Med. 2012;doi:10.1056/NEJMoa1200850.
- Klein NP, et al. Pediatrics. 2013;doi:10.1542/peds.2012-3836.
- Klein NP, et al. Pediatrics. 2016;doi:10.1542/peds.2015-3326.
- Koepke R, et al. J Infect Dis. 2014;doi:10.1093/infdis/jiu322.
- Winter K, et al. MMWR Morb Mortal Wkly Rep. 2014;63:1129-1132.
- For more information:
- Edward A. Bell, PharmD, BCPS, is a professor of pharmacy practice at Drake University College of Pharmacy and Health Sciences and Blank Children’s Hospital and Clinics, Des Moines, Iowa. He also is a member of the Infectious Diseases in Children Editorial Board. Bell can be reached at ed.bell@drake.edu.
Disclosure: Bell reports no relevant financial disclosures.