Two live, attenuated varicella zoster virus-containing vaccines are available in the United States for prevention of varicella: 1) a single-antigen varicella vaccine (VARIVAX, Merck & Co., Inc., Whitehouse Station, New Jersey), which was licensed in the United States in 1995 for use among healthy children aged > or = 12 months, adolescents, and adults; and 2) a combination measles, mumps, rubella, and varicella vaccine (ProQuad, Merck & Co., Inc., Whitehouse Station, New Jersey), which was licensed in the United States in 2005 for use among healthy children aged 12 months-12 years. Initial Advisory Committee on Immunization Practices (ACIP) recommendations for prevention of varicella issued in 1995 (CDC. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 1996;45 [No. RR-11]) included routine vaccination of children aged 12-18 months, catch-up vaccination of susceptible children aged 19 months-12 years, and vaccination of susceptible persons who have close contact with persons at high risk for serious complications (e.g., health-care personnel and family contacts of immunocompromised persons). One dose of vaccine was recommended for children aged 12 months-12 years and 2 doses, 4-8 weeks apart, for persons aged > or = 13 years. In 1999, ACIP updated the recommendations (CDC. Prevention of varicella: updated recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 1999;48 [No. RR-6]) to include establishing child care and school entry requirements, use of the vaccine following exposure and for outbreak control, use of the vaccine for certain children infected with human immunodeficiency virus, and vaccination of adolescents and adults at high risk for exposure or transmission. In June 2005 and June 2006, ACIP adopted new recommendations regarding the use of live, attenuated varicella vaccines for prevention of varicella. This report revises, updates, and replaces the 1996 and 1999 ACIP statements for prevention of varicella. The new recommendations include 1) implementation of a routine 2-dose varicella vaccination program for children, with the first dose administered at age 12-15 months and the second dose at age 4-6 years; 2) a second dose catch-up varicella vaccination for children, adolescents, and adults who previously had received 1 dose; 3) routine vaccination of all healthy persons aged > or = 13 years without evidence of immunity; 4) prenatal assessment and postpartum vaccination; 5) expanding the use of the varicella vaccine for HIV-infected children with age-specific CD4+ T lymphocyte percentages of 15%-24% and adolescents and adults with CD4+ T lymphocyte counts > or = 200 cells/microL; and 6) establishing middle school, high school, and college entry vaccination requirements. ACIP also approved criteria for evidence of immunity to varicella.

Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP).

A total of 11,356 subjects were reported to have varicella during the surveillance period, of whom 1080 (9.5%) had breakthrough disease. Children between the ages of 8 and 12 years who had been vaccinated at least 5 years previously were significantly more likely to have moderate or severe disease than were those who had been vaccinated less than 5 years previously (risk ratio, 2.6; 95% confidence interval [CI], 1.2 to 5.8). The annual rate of breakthrough varicella significantly increased with the time since vaccination, from 1.6 cases per 1000 person-years (95% CI, 1.2 to 2.0) within 1 year after vaccination to 9.0 per 1000 person-years (95% CI, 6.9 to 11.7) at 5 years and 58.2 per 1000 person-years (95% CI, 36.0 to 94.0) at 9 years. Conclusions A second dose of varicella vaccine, now recommended for all children, could improve protection from both primary vaccine failure and waning vaccine-induced immunity.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa064040

Loss of Vaccine-Induced Immunity to Varicella over Time

OBJECTIVE. In 1995, the United States was the first country to introduce a universal 1-dose childhood varicella vaccination program. In 2006, the US varicella vaccine policy was changed to a routine 2-dose childhood program, with catchup vaccination for older children. The objective of this review was to summarize the US experience with the 1-dose varicella vaccination program, present the evidence considered for the policy change, and outline future challenges of the program. METHODS. We conducted a review of publications identified by searching PubMed for the terms “varicella,” “varicella vaccine,” and “herpes zoster.” The search was limited to US publications except for herpes zoster; we reviewed all published literature on herpes zoster incidence. RESULTS. A single dose of varicella vaccine was 80% to 85% effective in preventing disease of any severity and >95% effective in preventing severe varicella and had an excellent safety profile. The vaccination program reduced disease incidence by 57% to 90%, hospitalizations by 75% to 88%, deaths by >74%, and direct inpatient and outpatient medical expenditures by 74%. The decline of cases plateaued between 2003 and 2006, and outbreaks continued to occur, even among highly vaccinated school populations. Compared with children who received 1 dose, in 1 clinical trial, 2-dose vaccine recipients developed in a larger proportion antibody titers that were more likely to protect against breakthrough disease and had a 3.3-fold lower risk for breakthrough disease and higher vaccine efficacy. Two studies showed no increase in overall herpes zoster incidence, whereas 2 others showed an increase. CONCLUSIONS. A decade of varicella prevention in the United States has resulted in a dramatic decline in disease; however, even with high vaccination coverage, the effectiveness of 1 dose of vaccine did not generate sufficient population immunity to prevent community transmission. A 2-dose varicella vaccine schedule, therefore, was recommended for children in 2006. Data are inconclusive regarding an effect of the varicella vaccination program on herpes zoster epidemiology.

Varicella prevention in the United States: a review of successes and challenges.

Varicella vaccine (Varivax, Merck) has been available in the United States since 1995. We reviewed published results of postlicensure studies of vaccine effectiveness. Among 19 studies, 17 reported on the effectiveness of vaccine received before exposure, and 2 reported on effectiveness after exposure. Studies used retrospective and prospective cohort, case-control, and secondary attack rate (household contact) designs. The majority of estimates assessed protection against clinically diagnosed varicella. One dose of varicella vaccine was 84.5% effective (median; range, 44%-100%) in preventing all varicella and 100% effective (mean and median) in preventing severe varicella. When administered after exposure, varicella vaccine was highly effective in preventing or modifying varicella. Although 1 dose of varicella vaccine has provided excellent protection, a higher degree of effectiveness is needed in order to interrupt transmission and to prevent outbreaks in settings with high contact rates. Monitoring the effectiveness of the newly recommended 2-dose childhood vaccine schedule for varicella vaccine is a priority.

Varicella vaccine effectiveness in the US vaccination program: a review.

CONTEXT: Several varicella vaccines are available worldwide. Countries with a varicella vaccination program use 1- or 2-dose schedules. OBJECTIVE: We examined postlicensure estimates of varicella vaccine effectiveness (VE) among healthy children. DATA SOURCES: Systematic review and descriptive and meta-analysis of Medline, Embase, Cochrane libraries, and CINAHL databases for reports published during 1995–2014. STUDY SELECTION: Publications that reported original data on dose-specific varicella VE among immunocompetent children. DATA EXTRACTION: We used random effects meta-analysis models to obtain pooled one dose VE estimates by disease severity (all varicella and moderate/severe varicella). Within each severity category, we assessed pooled VE by vaccine and by study design. We used descriptive statistics to summarize 1-dose VE against severe disease. For 2-dose VE, we calculated pooled estimates against all varicella and by study design. RESULTS: The pooled 1-dose VE was 81% (95% confidence interval [CI]: 78%–84%) against all varicella and 98% (95% CI: 97%–99%) against moderate/severe varicella with no significant association between VE and vaccine type or study design (P > .1). For 1 dose, median VE for prevention of severe disease was 100% (mean = 99.4%). The pooled 2-dose VE against all varicella was 92% (95% CI: 88%–95%), with similar estimates by study design. LIMITATIONS: VE was assessed primarily during outbreak investigations and using clinically diagnosed varicella. CONCLUSIONS: One dose of varicella vaccine was moderately effective in preventing all varicella and highly effective in preventing moderate/severe varicella, with no differences by vaccine. The second dose adds improved protection against all varicella.

Global Varicella Vaccine Effectiveness: A Meta-analysis

On November 18, 2003, the Oakland County Health Division alerted the Michigan Department of Community Health (MDCH) to a varicella (chicken pox) outbreak in a kindergarten-third grade elementary school. On December 11, MDCH and Oakland County public health epidemiologists, with the technical assistance of CDC, conducted a retrospective cohort study to describe the outbreak, determine varicella vaccine effectiveness (VE), and examine risk factors for breakthrough disease (i.e., varicella occurring >42 days after vaccination). This report summarizes the results of that study, which indicated that 1) transmission of varicella was sustained at the school for nearly 1 month despite high vaccination coverage, 2) vaccinated patients had substantially milder disease (<50 lesions), and 3) a period of > or =4 years since vaccination was a risk factor for breakthrough disease. These findings highlight the importance of case-based reporting of varicella and the exclusion of patients from school until all lesions crust or fade away. Information about recognizing vaccinated patients with mild cases should be disseminated to health-care providers, school administrators, and parents.

M. Boulton

Papers

Outbreak of varicella among vaccinated children - Michigan, 2003