Delicately and cautiously, health authorities in the United States and other countries are beginning to open up a difficult topic: Whether the extraordinary ongoing epidemic of whooping cough, the worst in more than 50 years, may be due in part to unexpected poor performance by the vaccine meant to prevent the disease.
That possibility, captured in several recent pieces of research — one published last night — is being raised so carefully because it might lead vaccine opponents to claim incorrectly that pertussis vaccination does not work. That fear contains a deep irony: The current vaccine, in use for about 20 years, replaced an older and more effective one that went out of use because vaccine critics charged it had too high a rate of side effects.
In the most recent research, a letter published Tuesday night in JAMA, researchers in Queensland, Australia examined the incidence of whooping cough in children who were born in 1998, the year in which that province began phasing out whole-cell pertussis vaccine (known as there as DTwP) in favor of less-reactive acellular vaccine (known as DTaP). Children who were born in that year and received a complete series of infant pertussis shots (at 2, 4 and 6 months) might have received all-whole cell, all-acellular, or a mix — and because of the excellent record-keeping of the state-based healthcare system, researchers were able to confirm which children received which shots. (NB: Queensland kids, like kids in the US, also receive boosters after the infant series, along with a final booster in their preteen years.)
The researchers were prompted to investigate because, like the US, Australia is enduring a ferocious pertussis epidemic. When they examined the disease history for 40,694 children whose vaccine history could be verified, they found 267 pertussis cases between 1999 and 2011. They said:
Children who received a 3-dose DTaP primary course had higher rates of pertussis than those who received a 3-dose DTwP primary course in the preepidemic and outbreak periods. Among those who received mixed courses, rates in the current epidemic were highest for children receiving DTaP as their first dose. This pattern remained when looking at subgroups with 1 or 2 DTwP doses in the first year of life, although it did not reach statistical significance. Children who received a mixed course with DTwP as the initial dose had incidence rates that were between rates for the pure course DTwP and DTaP cohorts.
This figure from the paper graphs the different results:
Pertussis is cyclical, with peaks occurring every three to five years, but the authors (who come from the University of Queensland’s Children’s Medical Research Unit), say the effect they found persisted through both “pre-epidemic and outbreak” periods. They acknowledge it is possible that circulating strains of the whooping-cough bacterium, Bordetella pertussis, may have changed over the decade-plus since the vaccines were switched, but say the most reasonable explanation is that the immune protection conferred by DTaP does not last as long as that from the older vaccine.
This possibility has been raised before. Last fall, at the annual ICAAC infectious-disease meeting, physicians from Kaiser Permanente Medical Center in San Rafael, Calif. reported that they were seeing an unexpectedly high amount of pertussis in fully vaccinated pre-teens who had not yet received their final booster dose. Of 171 kids diagnosed by PCR as having pertussis in 2010, 132 were between 8 and 14. They said at the time that the rate of pertussis in the pre-teen group was “almost 20-fold” that of more recently vaccinated pre-schoolers, but subsided again in children older than 12 who received their last booster — and they questioned whether the DTaP vaccine’s protection was waning earlier than expected and leaving the pre-teens vulnerable to infection. (The chart from their abstract is at right.)
Questioning the effectiveness of vaccines, in the midst of an epidemic and while they are under challenge from religious and “personal” exemptions, sounds like heresy — but in fact, the Centers for Disease Control and Prevention has raised the possibility just recently. The agency released a report July 20 on epidemics in Washington State (where cases are up 1,300 percent over last year) and and nationally. The report featured a widely circulated and dramatic graph of the epidemic curve — but it also included this less-reproduced graph, illustrating a difference in incidence between the whole-cell and acellular vaccine groups that resembles the data from Queensland:
Along with the graph, the report observed:
Acellular and whole-cell vaccines both have high efficacy during the first 2 years after vaccination, but recent changes in the epidemiology of pertussis in the United States strongly suggest diminished duration of protection afforded by childhood acellular vaccine (DTaP) compared with that of diphtheria and tetanus toxoids and whole-cell pertussis (DTwP) vaccine… Since the mid-2000s, the incidence of pertussis among children aged 7–10 years has increased. Moreover, the observed increase in risk by year of life from age 7–10 years suggests a cohort effect of increasing susceptibility as those children who exclusively received acellular vaccines continue to age.
In a media phone call that day, Dr. Anne Schuchat, director of the CDC’s National Center for Immunization and Respiratory Diseases, went over the reason for the 20-year-old switch that may have fueled these rising rates of disease. She said:
Wholecell pertussis vaccines are widely used in many parts of the world. But in the U.S., we have not been using them since 1997… The wholecell pertussis vaccines had a fairly high rate of minor and short-term side effects like fever and pain and swelling at the injection site. Those were fairly common reactions. And the acellular pertussis vaccines have a lower rate of the fever and transient side effects. There were also rare, but serious neurologic adverse reactions, including chronic neurologic problems that occurred among children that recently received wholecell vaccines. Studies have not been consistent about whether the vaccine actually caused those chronic neurologic problems. Yet there was substantial public concern about them and not just in the U.S., but in other countries. That led to a concerted effort to develop a vaccine with an improved safety profile.
Schuchat added:
In young children, we think that within a couple of years of vaccination the Dtap series is 95 percent protection. Five years later after the series, we think it wanes to 70 percent. That going down from 95 percent effectiveness to 70 percent may be why we see this increase in the older children or young teens.
There’s an important footnote to that math, though. The vaccines confer protection on a certain percentage of the population that has been vaccinated — but if a substantial proportion of the population is not vaccinated, then what would otherwise be a small gap in the wall of herd immunity potentially can become a gaping hole. If the protection conferred by the childhood vaccination is waning unexpectedly early, then reinforcing vaccination at all ages — in childhood and also through adult boosters — becomes more important than ever.
Cites:
- Sheridan SL, Ware RS, Grimwood K, Lambert SB. Number and Order of Whole Cell Pertussis Vaccines in Infancy and Disease Protection. JAMA. 2012;308(5):454-456. doi:10.1001/jama.2012.6364.
- Witt MA, Katz PH, Witt DJ, Marked Acellular Pertussis Vaccine Failure in 8-14 Year-olds in a North American Outbreak. 51st ICAAC, Chicago, September 2011.
- Pertussis Epidemic — Washington, 2012. MMWR. July 20, 2012 / 61(28);517-522.
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