AAP updated recommendations on varicella vaccine forthcoming

May 2007

After several publications suggesting that the duration of immunity following a single dose of varicella vaccine was waning, a definitive paper from CDC confirmed this.

The risk for breakthrough cases per 1,000 patients increased from 1.6 to 9 to 58.2 at one, five and nine years post-immunization. At the same time, the peak incidence shifted from a median of about five years prior to routine immunization to an older group, which was even greater for unvaccinated than vaccinated. The severity of illness also increased with respect to years since immunization, even taking into account the increase in severity with increasing age (N Engl J Med. 2007;356:1121) — a phenomenon that was reported to start at age 5 by Av Ross 45 years ago (N Engl J Med. 1962;267:369).

The AAP guidelines that will appear shortly will recommend routine immunization with two doses during childhood starting at between 12 and 15 months of age.

The second dose would be given at school entry but can be given as soon as three months after the first.

In the past, I leaned toward giving the second dose early, as the data from the one- and two-dose comparison indicated that most of the benefit from the second dose occurred in the years immediately after it was given (Pediatr Infect Dis J. 2004;23:132); 80% of the breakthrough cases in the one-dose group occurred in the first five years after the first dose, suggesting to me that these probably were failures of vaccination who were infected as soon as they were exposed.

These early cases disappear when a second dose is given, probably because the vaccine failures were eliminated by the second dose. However, these data were collected during a time when the age incidence may have been younger and children were infected in preschool.

Now this risk is diminished with the age incidence shifting to the school age group. It should be noted that the success rate from one dose in this paper is much higher than any comparable study and that only about half of the enrollees completed the nine-year study.

As the more recent paper suggests (N Engl J Med. 2007;356:1121), immunity after a single dose may be waning. It makes sense to give the second dose later at school entry to boost immunity and before school entry when the risk now is greater. The serologic data in the long-term observational study show an immediate increase in levels following the second dose, which declines to levels comparable to those achieved after a single dose by the second year after the second dose (Pediatr Infect Dis J. 2004;23:132).

What perhaps is more disconcerting is the observation that the antibody titers of both groups gradually rise for the duration of the study. These likely reflect the effect of boosting of both groups as a result of exposure to natural infection. One would anticipate that this will diminish as the number of vaccines increase.

Second dose goals

One of the major objectives of the second dose is to decrease school outbreaks, which are costly and inconvenient and have occurred in schools with as many as 95% of the students having had a single dose.

In the lead up to the recommendation for varicella vaccine, by far, preponderant saving was the prevention of parental lost wages because of exclusion of their children from school or out-of-home care (JAMA. 1994;274:375).

The average number of deaths annually in the United States between 1970 and 1994 was 90, half of which were in children — the target group of the vaccine program — and the remainder of which were in adults (J Infect Dis. 2000;282:383).

One should not lose sight of the fact that school absences, as well as deaths, hospitalizations and health care costs, have declined since the inception of the vaccine program (N Engl J Med. 2007;356:1121).

New recommendations

The new recommendations will include definitions of immunity, ie, those who do not have to be immunized. Written documentation of two doses or evidence of previous varicella should be verified by a health care professional.

Prenatal serology is recommended for pregnant adolescents and two doses of vaccine one month apart are recommended for seronegatives after pregnancy.

Our data from the study of 1,331 hospital workers, 163 of whom were aged younger than 30 years, revealed that only five of 26 with a negative history and one of nine with an uncertain history were actually found to be seronegative. All 163 who had a prior history were seropositive (Infect Control Hosp Epidemiol. 1999:20;355). Testing this group rather than relying on history is likely to be cost effective. I would recommend the latex agglutination test.

For children aged 1 through 12 years, measles-mumps-rubella-varicella (Proquad, Merck) is the preferred vaccine. It is not approved for anyone over the age of 12, however.

Unfortunately, this vaccine, which has a much greater varicella vaccine content than the monovalent type, will not be available for some time, as the demand for zoster vaccine — which also requires a large quantity of vaccine virus — has exceeded the ability to supply these vaccines.

Discontinuing routine immunization is not an option. Unprotected people will run the risk for getting varicella as adults when the morbidity is much greater.

As the chances for exposure decreases, the likelihood of growing to adulthood without being infected will be greater.

We may reach a point when varicella is “controlled.” At this point, we may have epidemics in colleges, as has been seen recently with mumps. Here, the morbidity has been significant. Varicella in adults should be avoided.