Pertussis Vaccines: Whole-Cell More Durable Than Acellular

Troy Brown

May 22, 2013

Teenagers who received 4 diphtheria, tetanus toxoids, acellular pertussis (DTaP) vaccines in the first 2 years of life had nearly a 6-fold higher risk of contracting pertussis than teenagers who received 4 diphtheria, tetanus toxoids, whole-cell pertussis (DTwP) vaccines, according to a case–control study of 1037 teenagers.

Nicola P. Klein, MD, PhD, from the Northern California Kaiser Permanente Vaccine Study Center in Oakland, and colleagues report their findings in an article published online May 20 in Pediatrics.

The study was conducted after a pertussis outbreak in California in 2010 to 2011. The study population included teenagers born from 1994 to 1999 who were given 4 pertussis-containing vaccines during the first 2 years of life. Cases that were pertussis polymerase chain reaction (PCR)-positive (n = 138) were compared with PCR-negative cases (n = 899) and Kaiser Permanente Northern California matched controls (n = 54,339).

Among 1037 individuals who were PCR tested, 234 (22.6%) were given all whole-cell vaccines, 197 (19.0%) were given a mix of whole-cell and acellular vaccines, and 606 (58.4%) were given all acellular vaccines. Among those who received a mix, 157 (79.7%) received 3 DTwP and then 1 DTaP vaccine, 12 (6.1%) had 2 DTwP and then 2 DTaP vaccines, 17 (8.6%) had 1 DTwP and then 3 DTaP vaccines, and 11 (5.6%) received some other combination of vaccines.

As the number of DTaP doses increased from 0 to 4, the percentage of positive PCR tests for pertussis increased significantly (P < .001 for trend).

The researchers compared case patients with PCR-negative control patients after adjusting for calendar time, sex, race, medical clinic, and vaccination status. Among those who received 4 DTaP vs 4 DTwP vaccines, the odds ratio (OR) of having a positive PCR test was 5.63 (95% confidence interval [CI], 2.55 - 12.46). Among those who received mixed DTwP/DTaP vs 4 DTwP, the OR was 3.77 (95% CI, 1.57 - 9.07). Results were similar when case patients were compared with Kaiser Permanente Northern California matched control patients.

The OR of a positive pertussis PCR test based on the number of DTaP doses received was 1.40 (95% CI, 1.20 - 1.62; P < .001) when compared with 4 doses of DTwP. On average, the risk for pertussis increased by 40% for each additional acellular dose received (and each additional dose of DTwP foregone) between the ages of 1 and 24 months.

Among the subgroup that had not received a Tdap booster, the adjusted OR for 4 DTaP vs 4 DTwP was 9.92 (95% CI, 1.31 - 75.31). Among those who had received the Tdap booster, the adjusted OR was 4.85 (95% CI, 1.92 - 12.21). This difference was not significant (P = .54 for the interaction term in the model comparing case patients with PCR-negative control patients).

Effect on Guidelines?

Tina Q. Tan, MD, an attending physician in the Division of Infectious Diseases at Ann & Robert H. Lurie Children's Hospital of Chicago and a professor of pediatrics at Northwestern University Feinberg School of Medicine in Chicago, commented on the study in an email interview with Medscape Medical News. Dr. Tan was not involved in the study.

"The acellular vaccines are effective at preventing pertussis; however, we are now learning that their duration of immunity is less than whole-cell pertussis vaccine," Dr. Tan said.

"[T]hey do not describe the persons with a positive PCR result, so some of these individuals may not have had any clinical symptoms, but because the area of the country was in a pertussis epidemic, they were tested for pertussis and the test came back positive," Dr. Tan said. "It is very difficult to interpret the clinical impact of this without clinical information."

Dr. Tan explained that the study won't change vaccination guidelines.

"[It] would not change the current practice guidelines given that we do not have whole-cell vaccine in this country and would not go back to using whole-cell vaccine given the adverse reactions associated with it," Dr. Tan concluded.

The study was funded by Kaiser Permanente. Dr. Klein and one coauthor report having received research support from GlaxoSmithKline, Sanofi-Pasteur, Pfizer, Merck, Novartis, and MedImmune. The pertussis vaccines purchased by Kaiser Permanente Northern California for this study were manufactured by (among others) GlaxoSmithKline, Wyeth (now Pfizer), Sanofi-Pasteur, and Merck. The other authors have disclosed no relevant financial relationships. Dr. Tan has received research funding from and has served as a consultant for Sanofi-Pasteur, Merck, and GlaxoSmithKline.

Pediatrics. Published online May 20, 2013. Abstract

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