Waning Vaccine-Induced Immunity to Varicella

Abstract & Commentary

By Jennifer L. Kruse and Philip R. Fischer, MD, DTM&H

Jennifer Kruse is a medical student at Mayo Medical School in Rochester, MN. Dr. Fischer is a professor of Pediatrics, Division of General Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN.

Jennifer Kruse and Dr. Fischer report no financial relationships relevant to this field of study.

Synopsis: Vaccine-induced immunity to varicella wanes over time, suggesting that a second dose of varicella vaccine may improve protection against infection. A second dose is recommended for individuals who previously received a single dose.

Source: Chaves, S.S., et al., Loss of vaccine-induced immunity to varicella over time. N Engl J Med 2007; 356: 1121-1129.

The incidence of chicken pox has decreased dramatically in the United States since implementation of a universal vaccination program in 1995. However, the question of whether or not there is waning immunity to varicella after one dose of vaccine led Chaves and colleagues to investigate the incidence of varicella in individuals vaccinated with one dose of varicella zoster virus (VZV) vaccine between 1995 and 2004.

The Varicella Active Surveillance Project was established by the CDC in collaboration with local and state health departments in 1995 to monitor cases of varicella in three communities: Antelope Valley, CA; Travis County, TX; and West Philadelphia, PA. The data from this active surveillance project were used by the authors to examine several variables related to varicella infection of vaccinated and unvaccinated subjects, including the effect of time since vaccination on the incidence of breakthrough varicella. Breakthrough varicella was defined as a diffuse maculopapular-vesicular rash without another apparent cause that developed more than 42 days after the subject had been vaccinated with VZV vaccine.

From January 1995 through December 2004, 11,356 subjects with varicella were identified. Within this group, 1,080 subjects (9.5%) had an onset of rash more than 42 days after vaccination. The rate of break-through varicella increased significantly with each year after vaccination, from 1.6 cases per 1,000 person-years within the first year after vaccination (95% CI, 1.2 to 2.0) to 20.4 per 1,000 person-years five years after vaccination (95% CI, 14.1 to 29.6) and 58.2 per 1,000 person-years nine years after vaccination (95% CI, 36.0 to 94.0).


Before the implementation of a universal varicella vaccination program in the United States, chickenpox was an illness that affected almost every U.S. child. Since 1995 the incidence of chickenpox in the United States has decreased dramatically.1 However, the incidence of varicella outside the United States remains high, as few countries routinely immunize children for varicella. Several industrialized countries now have universal vaccination programs in place, but most countries must prioritize other public health concerns above varicella or have chosen not to put resources into a universal vaccination program due to reservations about the costs and benefits of vaccination to the individual and the collective. 2 Consequently, most individuals in the world experience disease due to varicella zoster virus at some point in their lifetime. 3

The epidemiology of varicella in countries without varicella immunization programs varies depending on climate. In temperate climates, most cases of varicella occur before 10 years of age. The epidemiology is less well understood in tropical climates, where a relatively large proportion of adults are seronegative, and disease often presents at a later age.4 Adults traveling from tropical climates to temperate climates should be vaccinated for varicella if they show no evidence of immunity, as they are more likely to be seronegative and subsequently acquire varicella infection upon travel to temperate climates.

Another consideration in the epidemiology of varicella is the importation of VZV with recent immigrants and/or international adoptees. These individuals may have a varicella infection upon entry to the United States and subsequently serve as a source for varicella outbreaks among susceptible individuals.

Waning vaccine-induced immunity to varicella presents a public health challenge, as it may lead to a pool of susceptible older individuals at risk for more severe disease as a result of their age. It presents a problem for all individuals who have received only one dose of varicella vaccine and presents a particular problem for those within that group who plan to travel internationally. Individuals in the United States have a certain degree of protection due to low incidence of disease and evidence of herd immunity.5 However, chicken pox remains a universal childhood illness in most countries, suggesting that individuals with waning immunity to chicken pox who travel internationally are at higher risk of encountering varicella and thus are likely at an increased risk of contracting the disease. Therefore, it is important for individuals who have received just one dose of varicella vaccine to receive a second dose before traveling internationally.

The problem of waning vaccine-induced immunity has been addressed by the Advisory Committee on Immunization Practices, which recommends a routine two-dose varicella vaccination program for children and a second dose catch-up varicella vaccination for individuals who previously received one dose. ACIP also recommends routine vaccination of all healthy adults without evidence of varicella immunity.6

The clinical manifestations of varicella include a low grade fever that usually lasts 2-3 days, as well as lesions that begin early and crop up over several days. Because the lesions appear over several days, at any one point in time disparate lesions may be in different stages of development. Lesions appear first on the trunk and head, then move to the extremities including palms and soles, and are frequently found on mucus membranes, conjunctiva, and in the genital region.

The lesions present as papules that become vesiculated. The fluid within the vesicles usually becomes cloudy, and after the vesicles break, the lesions become crusted. The individual is contagious until all lesions have crusted over.

Complications of varicella zoster virus are uncommon but serious, and include secondary bacterial infection, varicella pneumonia, thrombocytopenia, varicella encephalitis, cerebellar ataxia, and Reye's syndrome.

Management of mild disease in otherwise healthy individuals is based on relieving discomfort and may include acetaminophen, antihistamines, and/or local applications such as calamine lotion, cool compresses, or cool baths to calm itching. Due to the risk of Reye's syndrome, it is important to avoid aspirin use in children with varicella. For immunocompromised patients with VZV, acyclovir should be administered, as it has been shown to reduce varicella-associated morbidity and mortality in this population if given within 24 hours of onset of rash. Varicella zoster immunoglobulin is used for prevention of varicella in immunocompromised individuals.7,8,9

We have the means to prevent disease due to varicella zoster virus, and we should be vigilant in ensuring immunity in all of our patients in order to protect them and to protect the public from morbidity and mortality due to varicella. All individuals who have not had disease due to VZV should receive two doses of vaccine. Individuals without a history of varicella illness could either undergo serologic testing for possible immunity to varicella, or they could be immunized. In particular, international travelers should receive appropriate immunizations for varicella before traveling. Patients from tropical climates who have no history of clinical chicken pox who are traveling to temperate climates could be immunized against varicella, as they are less likely to have acquired the disease in childhood. And, for patients who are recent immigrants and/or international adoptees, there should be high clinical suspicion for varicella if they present early with rash, as they may have imported a varicella infection that could lead to outbreaks in the community among susceptible individuals.


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