Pertussis Vaccine Update

Pertussis, or whooping cough, is often reported in the news when an infant dies. The disease causes severe bouts of coughing, and young infants are not physiologically or immunologically prepared to fight the infection. Because of their narrow windpipes, infants have trouble breathing during the coughing spells, sometimes turning blue; and most babies need the first three doses of pertussis vaccine to be sufficiently protected from infection. For these reasons newborns and young infants are at greater risk of hospitalization and death.

While a vaccine against pertussis has been available since the early 1900s, the history of the vaccine is complex and recently-identified strains of pertussis have made the current story more interesting.

Pertussis as a cause of disease

For the purposes of this discussion, a couple of points about the biology of pertussis are important to understand:

• Pertussis is caused by bacteria known as Bordetella pertussis.
• When pertussis bacteria infect epithelial cells that line the respiratory tract, a toxin, or poisonous chemical, is produced both at the site of infection and in the bloodstream, causing illness.
• As with many other respiratory infections, people can be infected with pertussis more than once, so even if they have had pertussis and survived, they are not immune for the rest of their lives.

Additional information about pertussis and the disease it causes can be found here:

• Pertussis information in VEC’s “A Look at Each Vaccine” Web page
• Pertussis: What you should know printable sheet [PDF, 285KB]
• Vaccines on the Go: What You Should Know is a free mobile app, available for Apple and Android, which contains diagrams showing the contagiousness of pertussis and an overview of the timeline for each stage of illness. Learn more about the app or download it today.

Early pertussis vaccine, known as the “whole-cell pertussis vaccine”

The first vaccine for pertussis was made in 1914. By the late 1940s the pertussis vaccine was combined with vaccines for diphtheria and pertussis, known as the DTP vaccine. Children received three doses of DTP, with each dose separated by about one month, and a booster dose at 1 year.

The DTP vaccine contained one protein that protected against diphtheria, one protein that protected against tetanus and about 3,000 proteins that protected against pertussis. Unfortunately, the vaccine had a high rate of side effects, most of which were attributed to the pertussis component of the vaccine. Mild side effects, such as pain and swelling as well as low-grade fever, fretfulness and drowsiness occurred in one-third to one-half of children who got this vaccine. Worse, about 1 of every 100 recipients experienced persistent, inconsolable crying, 1 of every 330 had a high fever, and about 1 of every 1,750 had seizures or experienced episodes in which they became floppy (lack of muscle control) and unresponsive. While all children recovered, these side effects were scary and led researchers to work toward a better understanding of pertussis infections and development of a second, safer pertussis vaccine.

Did you know?

During the mid to late 1940s, pregnant women were recommended to get pertussis vaccine in an effort to protect their newborn infants with maternal antibodies. 

Current pertussis vaccine, known as the “acellular pertussis vaccine”

A newer version of the pertussis vaccine became available in the 1990s. Instead of about 3,000 proteins, this acellular version contains only two to four pertussis proteins. The selected proteins are those that most commonly cause illness and allow the bacteria to infect cells in the respiratory tract. The newer version of the pertussis vaccine led to a dramatic decrease in the occurrence of side effects.

Infants and young children typically receive five doses of the vaccine known as DTaP; the first three doses, given during early infancy at 2 months, 4 months and 6 months, produce immunity. The latter two doses, typically around 15 to 18 months and again between 4 and 6 years of age, are considered booster doses — they “remind” the immune system that it has seen these disease-causing agents in the past.

Unfortunately, the medical community knew that as people got older they would become susceptible to pertussis again because the protection afforded by the vaccine given during infancy and before starting school (DTP or DTaP) was the same as the protection provided by a pertussis infection — short-term. However, the more doses of DTP or DTaP people received, the more likely they were to suffer severe (whole limb) swelling of the arm that was vaccinated. For this reason scientists designed the Tdap vaccine which contains lesser quantities of the diphtheria and pertussis vaccines; the lowercase letters in the nomenclature reflect this difference.

The Tdap vaccine is recommended for all adolescents around 11-12 years of age, and one time for adults. The exception to the recommendation for adults is that pregnant women should get the vaccine during each pregnancy, preferably during the period between 27 and 36 weeks’ gestation.

But, the pertussis vaccine story does not end there

Since the acellular pertussis vaccine became available, the U.S. has experienced increases in outbreaks of pertussis. While vaccine safety concerns have caused some to forego immunizations for their children, unvaccinated children in the community are not the main reason for these outbreaks. Researchers now understand that while the acellular pertussis vaccine has a better safety profile, it is less effective. In fact, studies have shown that children who got the DTP vaccine in infancy are less likely to get pertussis than those who got the DTaP vaccine. Further, even when older adolescents and adults get the Tdap booster vaccine, the protection decreases over time.

Additionally, a group of researchers found that some strains of pertussis that are causing disease no longer contain one of the proteins contained in the vaccines, known as pertactin. Pertactin is a protein that helps bacteria adhere to cells that line the respiratory tract. Because of this finding, some have questioned whether recent pertussis outbreaks are caused by these unusual bacteria. While researchers continue to study these strains, several pieces of information are reassuring: 

• Both vaccinated and unvaccinated children were found to have these strains, so vaccinated children do not appear to be at increased risk.
• Pertussis vaccines are still as protective as they were in the years before pertactin-negative strains were identified.
• Pertussis vaccines contain other proteins and these proteins have not changed, which is why the vaccine is still effective.

While these pertactin-negative strains should be monitored, they have not been found to be more dangerous than other strains of pertussis. Early data suggest pertactin-negative strains may be less virulent.

Conclusion

Pertussis vaccination is still the best choice for protecting ourselves and our children from pertussis. The vaccine is safe, but not perfect. Researchers should be urged to continue working toward a more effective pertussis vaccine. And, in the meantime, parents of young infants should make sure that visitors have had a Tdap booster and are not around the baby if they are ill. 

References

Atwell JE, Van Otterloo J, Zipprich J, Winter K, Harriman K, Salmon DA, Halsey NA, Omer SB. Nonmedical vaccine exemptions and pertussis in California, 2010. Pediatrics. 2013 Oct 1; 132(4):624-30.

Baxter R, Bartlett J, Rowhani-Rahbar A, Fireman B, Klein NP. Effectiveness of pertussis vaccines for adolescents and adults: case-control study. BMJ. 2013 Jul 17;347:f4249.

Klein, N. P.; Bartlett, J.; Rowhani-Rahbar, A.; Fireman, B.; Baxter, R. Waning protection after fifth dose of acellular pertussis vaccine in children. NEJM. 2012; 367: 1012-9.

Klein NP, Bartlett J, Fireman B, Rowhani-Rahbar A, Baxter R. Comparative effectiveness of acellular versus whole-cell pertussis vaccines in teenagers. Pediatrics. 2013 Jun;131(6):e1716-22.

Queenan AM, Cassiday PK, Evangelista A. Pertactin-negative variants of Bordetella pertussis in the United States. NEJM. 2013; 368: 583-4