Varicella Health Article

Prevention

The available varicella vaccines are a single antigen vaccine and a combination vaccine against measles, mumps, rubella, and varicella (MMRV). The live, attenuated varicella vaccine is available worldwide as Varivax (Merck, NJ, USA), Varilrix (GlaxoSmithKline, Rixensart, Belgium), and Okavax (Biken, Osaka Japan). The vaccine was developed in Japan. ¹³¹ All vaccines use the Oka strain of varicella-zoster virus, which was isolated from a healthy child with varicella and attenuated by sequential passage in cell culture. ³

The single-antigen varicella vaccine is licensed in various countries for use in healthy children who are either older than 9 months (Varilrix) or older than 12 months (Varivax and Okavax). The suggested vaccination schedule is one dose for children up to 12 years, and two doses, 4–8 weeks apart, for people 13 years and older. ^3,132,133 HIV-infected children with age-specific CD4 of greater than 15% or 25% can receive varicella vaccine in the USA ¹³³ and Europe respectively. In Europe, the varicella vaccine is licensed for use in immunocompromised patients with 1200 or more lymphocytes per μL blood. In healthy children, the seroconversion rate after one dose of live, attenuated varicella vaccine is 97–99%. ^122,123,133 About 87% of children achieve a gp ELISA level greater than 5 units (an approximate correlate of protection) following the first dose of Varivax vaccine; 99% achieve this level after the second dose. ¹²²

An MMRV combination vaccine (Proquad, Merck, NJ, USA) was licensed in the USA in 2005 for use in children aged 12 months to 12 years; and it is expected to be licensed soon in Europe and elsewhere. The vaccine contains a higher amount of varicella-zoster virus than does the monocomponent varicella vaccine, and the same amounts of measles, mumps, and rubella vaccine viruses as does MMR. Seroconversion rates are greater than 98% for these components after two doses of MMRV. ¹³⁴ A gp ELISA level of more than 5 units can be measured in about 90% of children after one dose of MMR; and 99% of children after two doses. ¹³⁴ Apart from a measles-like rash and fever 5–12 days after vaccination with MMRV, rates of other local and systemic adverse events for this vaccination schedule, and for concomitant MMR and varicella vaccine were much the same. ¹³⁴

Another MMRV candidate vaccine (Priorix-Tetra, GlaxoSmithKlein, Rixenart, Belgium) has been developed for use in children older than 12 months of age, and was licensed in Germany and Australia in 2006. In one study, two doses of this MMRV vaccine were at least as immunogenic as two doses of MMR and one dose of single-antigen varicella vaccine. ¹³⁵ All children in both vaccine groups had seroconverted to measles, rubella, and varicella after the second dose, and more than 98% had seroconverted to mumps in both groups. ¹³⁵ This MMRV vaccine did not induce increased rates of local or systemic adverse events compared with separate administration of the MMR and single-antigen vaccines, apart from an increased rate of low-grade fever (<39°C) after the first dose of MMRV (68% vs 49% after separate vaccine doses). ¹³⁵

Comparison between studies of varicella vaccine efficacy is difficult or impossible. ³ Only two randomised controlled clinical trials have examined efficacy in healthy children. ^136,137 In the US, trial investigators compared varicella vaccine (17,000 pfu but erroneously reported as 8700 pfu) with placebo given to children aged 1–14 years, and showed that the vaccine was 100% effective with 9 months of follow-up. ^3,136 In the European trial, high titre (10,000–15,850 pfu) and low titre (630–1260 pfu) vaccine were compared with placebo given to children 10–30 months old, and followed up for a mean of 29 months. ¹³⁷ On the basis of the reported attack rates, vaccine efficacy was calculated by these authors as 88.2% for the high titre vaccine and 55.3% for the low titre vaccine. ¹³⁷

Post-licensure studies are easily compared since they use standard vaccine doses (of ≥1350 pfu at expiration). A decade of use of Varivax in the universal vaccination programme in the USA has produced post-licensure data from more than 15 studies. They show that varicella vaccine is usually 80–85% effective (with a range of 44–100%), in prevention of all varicella disease and more than 95% effective in prevention of moderate and severe disease (table ). For Varilrix, the three studies that have been done estimated vaccine effectiveness as 88%, 92%, and 20%. ^151,152 Most varicella cases in vaccinees are mild, suggesting suboptimum induction of immunity. ¹⁵⁴ However, these mild cases can be contagious. ¹⁷ Protective effectiveness in the range of 81–86% has been maintained for 2–8 years postvaccination in the USA, with reduced opportunity for boosting through exposure to varicella-zoster virus in recent years. ^145,155

In prelicensure clinical trials, and post-licensure surveillance with more than 50 million doses used in the USA and elsewhere, varicella vaccine has proven safe in susceptible children and adults. ^{136,156–158} Serious risks are rare; 2.8 cases have been reported per 100,000 doses of vaccine distributed. ¹⁵⁷ In post-licensure safety surveillance, identification of vaccine virus has allowed accurate description of adverse events. The vaccine virus has occasionally been transmitted from healthy vaccinees to healthy recipients. ¹⁵⁹ Also rarely, in children with immunodeficiencies that were undiagnosed at the time of vaccination, the vaccine has caused severe infections or disseminated disease, including pneumonia. ^160–162

Severe adverse events—including acute anaphylaxis, ataxia, encephalitis, stroke, idiopathic thrombocytopenic purpura, and pneumonia—have been reported after vaccination in healthy children, but all are rare. ^163,164 Although few such events have been attributed to the vaccine virus, they represent a plausible risk for this live, attenuated virus. ¹⁶² Of note, one post-licensure safety evaluation of almost 90,000 vaccinated people reported no cases of ataxia, encephalitis, or other severe complications. ¹⁵⁸ No deaths have been attributed to the vaccine virus. Herpes zoster can result from vaccine virus, but this seems to happen at a lower frequency in both immunocompromised and healthy vaccine recipients than in those who contracted varicella naturally. ^3,158,165

Passive immunisation with varicella zoster immunoglobulin can sometimes prevent or more usually ameliorate clinical varicella in people who are exposed to the virus at high risk of severe disease. ^132,166 It is frequently used for exposed people for whom varicella vaccine is contraindicated, including immunocompromised susceptible children, neonates whose mothers acquire varicella from 5 days before to 2 days after birth, adolescents, and adults, as well as premature infants and pregnant women. Various formulations of varicella zoster immunoglobulin are available in the USA (where it is an investigational drug), ¹⁶⁷ and in Canada, Australia, and Europe. Most require administration within 96 h of exposure, but the UK product can be used for up to 7 days after exposure. Some trials in healthy children have shown that high-dose acyclovir, given orally 7–14 days after exposure for 5 to 7 days, is effective in prevention or modification of varicella. ^168–170 Data on the postexposure efficacy of acycolivir in immunocompromised children are sparse. However, high-dose acyclovir might be useful in addition to varicella zoster immunoglobulin or alone if the recommended time window for giving varicella zoster immunoglobulin has passed in this high risk group. Varicella vaccine is also effective postexposure and can prevent or modify illness in up to 90% of exposed people if given within 3 days, and in 67% of people if given within 5 days of exposure. ^18,171,172