Varicella vaccine: much learned and more still to know

March 2002

---Philip A. Brunell, MD

Varicella vaccine (Varivax, Merck) was licensed in 1995. Due to the delay in the publication of recommendations for its use, there was a lag of about a year before there was significant use of the vaccine. Now, we have substantial experience with it and it is fun to reflect on the predictions, which were made before licensure. Has it reduced morbidity and cost?

The cost of the vaccine was a surprise at the time but it should not have been. Varicella vaccine had a long “gestation period” during which many clinical trials were performed with different lots of vaccine varying one from the other in the amount of virus, among other things. The vaccine was also difficult to manufacture, and stability of the vaccine during shipment and storage were some of the concerns. The estimates of dollars saved by a vaccine program was calculated assuming a dose would cost $35 [JAMA. 1994;271:375]. I cannot recall a vaccine which cost less after licensure than what had been projected before licensure. The cost savings were projected to be accrued as a consequence of decreased loss of time from work by parents whose children were excluded from school when they had chickenpox.

Breakthrough cases

During the clinical trials, it was recognized that there would be vaccine breakthroughs but that these would be much milder than the natural disease. It was found in prelicensure trials that about 12% of these breakthrough cases would transmit varicella to immunized household contacts [Pediatrics. 1993;91:7]. Now, we are faced with the question of whether these children should be permitted to attend school and, if not, when can they be readmitted? The proportion of modified varicella in vaccinated children is expected to increase in coming years as the number of children immunized increases. We must not forget, however, that most children who have received varicella vaccine will be fully protected and will not get chickenpox; therefore, their absence from school will be prevented.

Setting cost aside, modified chickenpox is much more bearable by children and parents. In one series, 54% were asymptomatic, except for rash, which was represented by far fewer lesions than natural infection [Pediatrics. 1993;91:7].

Perhaps, the unforeseen consequence of routine immunization with varicella vaccine is deciding which rashes in vaccine recipients represent modified varicella and which are unrelated. Some occurring shortly after immunization will be caused by vaccine. The latter are not likely to transmit infection, although this has happened in rare instances.

Accurate diagnosis

Determining which children are likely to transmit wild varicella virus to contacts becomes an important issue if children with modified chickenpox are to be excluded from school. In one study of several pediatric practices (N Engl J Med. 2001;344:955), the diagnosis of varicella was made over the phone in 65% of the cases. Specimens were collected from these children at their homes. Only 74% of the total number of cases diagnosed as varicella and had adequate specimens, were confirmed by PCR to be chickenpox.

In another study, about one-third of cases diagnosed by physicians were thought not to be varicella when seen by specialists (Pediatrics. 1993;91:17). Since the introduction of vaccine, more parents may wish to have their child evaluated clinically to determine the etiology of the eruption. There is a danger that children misdiagnosed as chickenpox may not receive the vaccine, as their parents may believe they are immune. Although the number of breakthroughs may be less than the previous number of varicella cases, more children may need to be seen for rashes to make sure it’s not chickenpox.

Prior to licensure, projections of the vaccine’s impact were made using several scenarios. Several assumptions about the proportion of the population that would receive the vaccine, the spread of infection to contacts from breakthrough cases, the proportion of vaccine failures, the duration of immunity and other factors.

If 97% of children are immunized, varicella would virtually disappear. When 70% of children are immunized during the second year of life and 97% are immunized by school entry, which we have not yet attained, there would be a significant shift of cases to older individuals including women in the child-bearing age group

The reason for this is that the unimmunized children stand a good chance of growing into adults without having the vaccine or varicella. In adulthood the illness is much more severe. Those who have received the vaccine protect the unimmunized against natural infections. This seems to be the case as the number of cases in children younger than 1, ie, too young to be immunized, has decreased each year.

In practice, the vaccine has been very effective. The number of cases in areas that have surveillance programs has dropped precipitously and most of the cases of vaccine failures have been mild. Most impressive is the decrease of between 50%-80% in hospitalization for complications of chickenpox in areas where this has been studied. The complications of varicella, which appear to be prevented, were much more common than the adverse events of immunization. In addition, the vaccine appears to be very safe (JAMA. 2000;284:1271), and there are no unexpected surprises in terms of safety of the vaccine.

We now have several years and almost 30 million doses of experience and we have learned a great deal. Still, there is much to be learned. There is no indication that vaccinees have a greater risk of zoster, in fact it appears to be less, or that they will lose their vaccine-induced immunity. Not immunizing increases the likelihood of children growing to adult life without immunity to varicella. Immunization now reduces the risk of severe varicella, hospitalization and loss of time from school.