An update on varicella immunization

April 2006

There have been a number of recommended changes in both passive and active immunization against varicella that one should be aware of.

Varicella zoster immune globulin (VZIG; Varizig, Cangene) no longer is available but there now is an alternative albeit a rather cumbersome one. The measles-mumps-rubella-varicella (MMRV; Proquad, Merck) vaccine finally has been licensed, and there are recommendations for its use and storage that are important to note. Finally, there are broadened recommendations for the use of varicella vaccine.

The immunization rate of people aged 19 to 36 years in the United States had reached 85% in 2003, but it is uneven nationally.

Health officials have set their sights on a national immunization rate of 90% by 2010, together with the elimination of varicella defined as prevention of endogenous transmission. Since vaccine licensure, there has been a striking decline in both cases and deaths, although there are many indications that there has been a plateau reached during the past few years.

Two Pennsylvania vaccinees receiving steroids died. Although most outbreaks that have been investigated have revealed vaccine protection between 70% and 100%, several studies have reported efficacy of 44% to 59%, some with a reduction in efficacy following an increased interval since immunization. It is important to note that most of the cases have been mild. The more severe cases are more likely to be contagious, which has led to transmission in classrooms and the households of the affected children. It is feared, however, that mild cases that had been missed may be responsible for transmission. Awareness that mild cases may transmit infections should prompt us to inspect children carefully for evidence of varicella when it is prevalent in the school or community.

To achieve the 2010 goal, several changes have been recommended but not officially released at this time. There is a movement toward a second-dose schedule, in order to address concerns about the accumulation of susceptible older adults who are expected to suffer greater morbidity than children. Although there was little difference found in antibody titers in those receiving one or two doses after 10 years, there was about a 5% increase in protection. Whether this was due to the elimination of no takes by giving a second dose or by increasing duration of protection is unclear. It should be noted that the efficacy in these studies was much greater than generally reported (Pediatr Infect Dis J. 2004:23;132).

A routine second dose for all children between 4 and 6 years of age was not recommended at this time. Probably the most significant of the recommendations is that those who have received a single dose of vaccine receive a second at least three months after the first, during an “outbreak.” Outbreak is not clearly defined in the proposed recommendation, but presumably this would be mainly directed at children in out-of-home care or schools. At the same time, it is recommended that immunization requirements should include all levels of education up to and including college.

The major change, as I see it, is the recommendation that all individuals without evidence of immunity older than 13 years of age receive two doses at least a month apart.

The lesson to be gained here is to immunize everyone appropriately prior to this time when only a single dose is recommended. The recommendation will result in immunizing a significant portion of the adult population. Immunity is defined as documented evidence of appropriate immunization, laboratory evidence of immunity, a history of zoster or born in the United States prior to 1966. Varicella tends to occur in older age groups, sparing children in some tropical countries. For people older than age 40 born outside the United States, they should have a history of typical disease or laboratory-confirmed or physician-diagnosed atypical disease. There is a caveat about diagnosis of mild disease, which may be confused with other illnesses after the introduction of the vaccine in the mid-90s.

There also is a recommendation about evaluation of immunity during pregnancy and immunizing postpartum women who are found to be susceptible. Finally, the criteria for immunizing those who have HIV have been liberalized to include children with CD4 percentages greater than 15%. MMRV is not recommended for children with HIV at this time. Pretesting of eligible adults for HIV prior to immunization has not been mentioned, but probably is not recommended.

MMRV recommendations

How does MMRV, which was approved by the FDA in 2005 for children aged 1 to 12 years (www.cdc.gov/mmwr/preview/mmwrhtml/mm5447a4.htm) fit into this scheme? One thing that is important to note is the storage requirements are less than 5°F for up to 18 months. MMRV is preferred for those children who require initial immunization with both MMR and varicella vaccines. It can be used if only one of the components is required, eg in an outbreak, when the others have been given previously. Parenthetically, the amount of varicella vaccine in MMRV is 3.99 log₁₀, below the amount indicated in the reference cited.

As many of you who have tried to obtain VZIG recently, know, manufacture in the United States has been discontinued. Varizig, which is manufactured in Canada, is a comparable product with the same indications. However, it is an investigational drug distributed by FFF Enterprises, which can be reached at 800-843-7477 (Temecula, Calif.). A central institutional review board has approved it, but local approval also may be needed in some situations (www.cdc.gov/mmwr/preview/mmwrhtml/mm5508a5.htm).

Stocking may facilitate its use by local pharmacies. All of this takes time and may delay the administration beyond the 96 post-exposure point.

Alternatively, one can give IV immunoglobulin (IVIG) although the titer of various lots may vary in varicella zoster vaccine (VZV) titers as there is no requirement at this time for IVIG to have a specific VZV titer. IVIG carries with it some potential adverse events, a lot of inconvenience and postponement of live vaccines for months. Finally, there is the off-label use of acyclovir starting seven days following exposure. This has been very effective in normal children (Pediatrics. 1993:92;219-222).

These recommendations will not become official until published in Morbidity and Mortality Weekly Report. Although there is no recommendation for a routine second dose of varicella vaccine, there is clearly movement in this direction.