Study shows drop-off in kids' pertussis vaccine protection

Nov 28, 2012 (CIDRAP News) – The largest study so far exploring gaps in acellular pertussis vaccine protection in kids found that their risk of getting sick increased as time passed after the final dose, according to researchers who examined the role of the vaccine during California's 2010 pertussis epidemic.

The case-control study, which spanned 15 California counties, also found that kids who got sick with pertussis were less likely to have received all five doses of the acellular pertussis vaccine (DTaP) series. The group published its report in today's Journal of the American Medical Association (JAMA).

New data about the drop-off in protection comes amid mounting evidence of waning protection with the acellular vaccine that the United States and other countries embraced after the late 1990s. Health officials recommended the switch, because the whole-cell version caused a fairly high rate of minor side effects.

Earlier this year the US Centers for Disease Control and Prevention (CDC) warned that the United States was facing its worst pertussis year in decades, and experts suspect that the waning protection in kids could be among the factors fueling outbreaks. Pertussis cases have been especially numerous in states such as Washington and Colorado, which have declared epidemics this year.

In the JAMA study, researchers analyzed 682 cases of suspected, probable, and confirmed pertussis in children ages 4 to 10 who were seen at clinics in 15 counties between January and Dec 14, 2010. Their investigation included 2,016 controls in the same age-group who were recently treated by clinicians for other conditions.

Researchers looked at children's illnesses and vaccination histories to tease out associations between pertussis and receiving the five-dose series, to gauge vaccine effectiveness (VE), and to calculate the time between the fifth dose and illness onset. Because the control group skewed younger, possibly because of well-child visits or because parents were more likely to seek care for younger children, researchers drew a 200-person random sample group from the controls to conduct a separate analysis.

They found that kids who got sick with pertussis had lower odds of having received the five-dose vaccine series (odds ratio [OR], 0.11, 95% confidence interval [CI] 0.06 to 0.21) and that odds of getting sick increased with the passage of time after the last vaccine dose, suggesting a progressive decline in vaccine effectiveness. The odds ratio was 0.02 with a VE of 98% during the first 12 months after the fifth dose and increased to 0.29 with a VE of 71% by 60 months or longer, according to the study.

The separate analysis that was done to ensure even age distribution showed little difference in the findings.

The team suggested that waning immunity following DTaP vaccination may have contributed to a larger pool of susceptible patients. "In periods of increased pertussis transmission, the burden of disease attributable to the vaccinated but susceptible population is high," they wrote.

Some sources have suggested a possible mismatch between the vaccine and circulating pertussis strains could be playing a role in the epidemic. But the authors said the age-related illness spikes at ages 5 and 6 years and again at ages 7 to 10, along with the high short-term vaccine effectiveness of 98.1%, argue against the vaccine mismatch suspicions.

The pertussis increase in children ages 7 to 10 isn't unique to California, and national surveillance data will help clarify whether the change from the whole-cell to the acellular vaccine explains the trends, the researchers added.

In an editorial in the same issue of JAMA, Eugene Shapiro, MD, professor in the departments of pediatrics, epidemiology, and investigative medicine at Yale University School of Medicine, wrote that the findings agree with two smaller case-control studies conducted during California's pertussis epidemic that suggested vaccine immunity waned in preadolescents. He noted that the authors of the new larger study were able to calculate the odds ratio for infection, which allowed them to estimate the vaccine's effectiveness.

Shapiro wrote that the studies are observational and don't show a definitive cause, but data from experimental studies on the duration of protection from the acellular vaccine aren't likely to be available soon.

He commented that other factors could be playing a role in the resurgence of pertussis, such as more sensitive diagnostic tests, increased awareness of the disease, and a pool of susceptible adults and adolescents providing a large reservoir for maintaining B pertussis in the population. "Mounting evidence that more children aged 7 to 10 years are susceptible and may be expanding this pool adds to an already existing problem," he wrote.

Though the acellular vaccine might not be ideal, it is still effective, and the current incidence of pertussis is low when compared to the prevaccine era, Shapiro wrote. Improved vaccination strategies might be one way to curb the disease, such as immunizing all pregnant women and others who have close contact with babies too young to be immunized.

He noted that other options might include shortening the period between primary and booster doses or considering a return to the whole-cell vaccine for the first dose.

Misegades LK, Winter K, Harriman K, et al. Association of childhood pertussis with receipt of 5 doses of pertussis vaccine by time since last vaccine dose, California, 2010. JAMA 2012 Nov 28;308(20):2016-32 [Full text]

Shapiro ED. Acellular vaccines and resurgence of pertussis. (Editorial) JAMA 2012 Nov 28;308(20):2049-50 [Extract]

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