Literature Commentary by Dr. John G. Bartlett: Viral Infections, January 2008

John G. Bartlett, MD


January 09, 2008

Varicella/Herpes Zoster

Marin M, Güris D, Chaves SS, et al. Prevention of varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2007;56(RR04):1-40. The following is an updated review of new guidelines for varicella vaccination and the background that led to these decisions.

Prevaccine Experience: Prior to the varicella vaccine, which was introduced in 1995, varicella was a universal childhood disease in the United States, and national seroprevalence data for 1988-1994 showed that 99.6% of adults over 40 years old were immune. At that time, the most common complications requiring hospitalization were skin and soft tissue infections, especially group A streptococcus, pneumonia, and encephalitis. On average, there were 105 deaths per year. Varicella was recognized as having adverse consequences to the fetus, with an estimated average of 44 cases of the congenital varicella syndrome per year. Adults over 20 years old were more seriously ill and 15 times more likely to be hospitalized than children.

Vaccines: A varicella vaccine was introduced in 1995 and was recommended for children age 12-18 months with catch-up vaccination of susceptible children aged 19 months to 12 years; the vaccine was also recommended for susceptible persons who have close contact with those considered at high risk for serious complications, including healthcare workers and family contacts of immunosuppressed people.

Postvaccine Era: During the period 1993-2001, the number of hospitalizations for varicella decreased by 75% and the number of deaths decreased by 66%.

During 2001-2005, outbreaks were reported in elementary schools, including those with vaccination rates of 96% to 100%. The disease was mild and each outbreak lasted about 2 months. Index cases were in vaccinated students; the attack rate in these students was 11% to 17%.

Surveillance for herpes zoster in the prevaccine era estimated that 15% to 30% of the general population have herpes zoster during their lifetime. This risk did not change significantly after the vaccination program was initiated in 1995 on the basis of multiple studies and surveillance data.

Immune Response: Rates of breakthrough disease in children were lower when the antibody titer was > 5 glycoprotein enzyme-linked immunosorbent assay (gpELISA) units; the relative risk was 3.5 for children with a 6-week postvaccination antibody titer of < 5 gpELISA units compared with those with a titer ≥ 5 gpELISA units. The prelicense studies indicated that a single dose of the vaccine was 70% to 90% effective in preventing the disease and 95% effective in preventing severe disease at 7-10 years after vaccination. With 2 doses given 3 months apart, the efficacy at 10 years was 98.3% and 100% effective against severe disease.

Evidence of Immunity: The Advisory Committee on Immunization Practices (ACIP) considers the following to be evidence of immunity:

  • Documented vaccination (only written documentation with the date of administration is considered valid);

  • Laboratory evidence of immunity or laboratory confirmation of disease; it is noted that commercial assays are often used but often lack sensitivity and may give false-negative results;

  • Birth in the United States before 1980 except for healthcare personnel, pregnant woman, and immunocompromised persons;

  • A verified history or diagnosis of typical disease by a healthcare provider; and

  • Herpes zoster verified by healthcare provider.

Transmission of Vaccine Virus: Because this is a live virus vaccine, there has been concern about transmission, particularly to susceptible hosts. However, since licensure, over 55 million doses of varicella vaccine have been distributed and there is polymerase chain reaction (PCR)-documented transmission from only 5 persons to 6 secondary contacts.

2007 Recommendations for Adults: Adults without evidence of immunity on the basis of the criteria summarized above should receive 2 doses of varicella vaccine 4-8 weeks apart. High priority should be given to the following:

  • Healthcare workers;

  • Household contacts of immunosuppressed persons;

  • Persons who live or work where there is a risk for transmission of varicella, including teachers, day care employees, and both residents and staff in institutional settings;

  • Persons who live or work in environments in which transmission has been reported, such as college students, inmates, etc.;

  • Nonpregnant women of childbearing age; and

  • Adults and adolescents living in households with children.

Special considerations include patients with HIV infection, antenatal screening, and outbreak setting and postexposure. These recommendations are summarized in Table 1 .

Kimberlin DW, Whitley RJ. Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med. 2007;356:1338-1343. This is a "Clinical Therapeutics" review in The New England Journal of Medicine by noted authorities.

Natural History: Herpes zoster develops in about 30% of people at some time in their life. Herpes zoster is 8-10 times more likely in persons over 60 years of age and occurs in about half of persons over 85 years. Immunosuppression is also a risk factor. Complications include postherpetic neuralgia, which is most common in persons older than 60 years and can last for weeks, months, or years. Other complications include encephalitis, myelitis, cranial-nerve palsies, and peripheral neuropalsies[1]

Vaccine Trial:The vaccine trial included 38,546 participants age 60 years or older who were randomized to receive vaccine or placebo and were followed for 3 years. The results showed a 51% decrease in the frequency of herpes zoster, a 67% reduction in the rate of postherpetic neuralgia, and a slight decrease in the duration of pain. These results are shown in Table 2 .

Cost-Effectiveness: Analyses of the cost-effectiveness of vaccination are based on a "societal perspective cost," which is an assumed drug charge of $150 and a vaccine cost of $15,000-$35,000/quality-adjusted life-year gained." This means that approximately 17 people would need to be vaccinated to prevent 1 case of herpes zoster, and 31 would require vaccination to prevent 1 case of postherpetic neuralgia.

Adverse Effects of the Vaccine: Varicella-like rashes developed at the injection site in 0.1% of vaccine recipients and 0.04% of controls. Local reactions with erythema and tenderness occurred in about 35% of patients, swelling in 26%, and pruritus in 7%.

Guidelines: In October 2006, the ACIP recommended zoster vaccine for all adults over 60 years. It is not necessary to determine whether there was previous chickenpox because all patients in this age category were born before 1980, when chickenpox was universal. It is noted that the protection afforded persons 60-69 years old is significantly better than for those over 70 years. The authors raise the issue of a potentially better protective effect if given to people at age 50-59 years, which would require off-label use but might get a better immune response.

Comment: Another cost-effectiveness analysis concluded that the incremental costs of the vaccine were $44,000 per quality-adjusted life-year saved for a 70-year-old woman and $191,000 per quality-adjusted life-year saved for an 80-year-old man. This analysis was particularly sensitive to the vaccine cost.[2] However, it is clear that cost-effectiveness varies substantially with age, so these authors warn that in those who are more elderly, the cost often exceeds $100,000 per quality-adjusted life-year saved and that age should be considered with the vaccine recommendations.


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