Do Vaccines Cause Vaccine-Strain Viral Reactivation?

Conclusion | Epidemiological Evidence | Proposed Biological Mechanism | Archives | References


Conclusion

Varicella vaccines can rarely cause zoster due to vaccine-strain viral reactivation. Other vaccines currently routinely recommended to the general population in the U.S.* do not cause vaccine-strain viral reactivation.

Epidemiological Evidence

The 2012 report by the Institute of Medicine (IOM), now called the National Academy of Medicine (NAM), described one study assessing varicella vaccination with vaccine-strain viral reactivation [1]; however, it did not provide convincing evidence due to a lack of validity and precision [2]. One large randomized controlled trial published since the 2012 IOM report and conducted in ten European countries found one unconfirmed case of herpes zoster infection and one papular rash out of 4976 recipients of either the MMR vaccine Priorix and the varicella vaccine Varilrix or the combination MMRV vaccine Priorix-Tetra, all vaccines not used in the U.S. Both of these serious adverse events were reported as recovered or resolved [3].

Proposed Biological Mechanism

Varicella vaccines are live attenuated viral vaccines, and are therefore able to replicate in the body. Generalized rash is reported in 4-6% of recipients. Systemic reactions are uncommon but possible. Mild zoster illness (shingles) resulting from a latent infection with varicella vaccine virus has been reported. Immunodeficiency is a contraindication for most live vaccines, including varicella vaccine. For more information, see the Varicella summary.

The 2012 IOM report described cases of vaccine-strain viral reactivation after varicella vaccination [4-23], and concluded that these cases together presented strong mechanistic evidence supporting an association [2]. In immunodeficient persons, vaccine-strain viral reactivation can result in meningitis [4, 9, 21-23] or encephalitis [11, 20].

References

1. Donahue JG, Kieke BA, Yih WK, et al. Varicella vaccination and ischemic stroke in children: is there an association? Pediatrics 2009;123:e228-34.
2. Institute of Medicine. In: Stratton K, Ford A, Rusch E, Clayton EW, eds. Adverse Effects of Vaccines: Evidence and Causality. Washington (DC): National Academies Press (US); 2012.
3. Prymula R, Bergsaker MR, Esposito S, et al. Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine versus one dose of monovalent varicella vaccine: a multicentre, observer-blind, randomised, controlled trial. Lancet 2014;383:1313-24.
4. Galea SA, Sweet A, Beninger P, et al. The safety profile of varicella vaccine: a 10-year review. J Infect Dis 2008;197 Suppl 2:S165-9.
5. Sharrar RG, LaRussa P, Galea SA, et al. The postmarketing safety profile of varicella vaccine. Vaccine 2000;19:916-23.
6. Wise RP, Salive ME, Braun MM, et al. Postlicensure safety surveillance for varicella vaccine. Jama 2000;284:1271-9.
7. Angelini P, Kavadas F, Sharma N, et al. Aplastic anemia following varicella vaccine. The Pediatric infectious disease journal 2009;28:746-8.
8. Bryan CJ, Prichard MN, Daily S, et al. Acyclovir-resistant chronic verrucous vaccine strain varicella in a patient with neuroblastoma. The Pediatric infectious disease journal 2008;27:946-8.
9. Chaves SS, Haber P, Walton K, et al. Safety of varicella vaccine after licensure in the United States: experience from reports to the vaccine adverse event reporting system, 1995-2005. J Infect Dis 2008;197 Suppl 2:S170-7.
10. Ghaffar F, Carrick K, Rogers BB, Margraf LR, Krisher K, Ramilo O. Disseminated infection with varicella-zoster virus vaccine strain presenting as hepatitis in a child with adenosine deaminase deficiency. The Pediatric infectious disease journal 2000;19:764-6.
11. Goulleret N, Mauvisseau E, Essevaz-Roulet M, Quinlivan M, Breuer J. Safety profile of live varicella virus vaccine (Oka/Merck): five-year results of the European Varicella Zoster Virus Identification Program (EU VZVIP). Vaccine 2010;28:5878-82.
12. Ihara T, Kamiya H, Torigoe S, Sakurai M, Takahashi M. Viremic phase in a leukemic child after live varicella vaccination. Pediatrics 1992;89:147-9.
13. Jean-Philippe P, Freedman A, Chang MW, et al. Severe varicella caused by varicella-vaccine strain in a child with significant T-cell dysfunction. Pediatrics 2007;120:e1345-9.
14. Kraft JN, Shaw JC. Varicella infection caused by Oka strain vaccine in a heart transplant recipient. Arch Dermatol 2006;142:943-5.
15. Kramer JM, LaRussa P, Tsai WC, et al. Disseminated vaccine strain varicella as the acquired immunodeficiency syndrome-defining illness in a previously undiagnosed child. Pediatrics 2001;108:E39.
16. Levy O, Orange JS, Hibberd P, et al. Disseminated varicella infection due to the vaccine strain of varicella-zoster virus, in a patient with a novel deficiency in natural killer T cells. J Infect Dis 2003;188:948-53.
17. Waters V, Peterson KS, LaRussa P. Live viral vaccines in a DiGeorge syndrome patient. Arch Dis Child 2007;92:519-20.
18. Chan Y, Smith D, Sadlon T, Scott JX, Goldwater PN. Herpes zoster due to Oka vaccine strain of varicella zoster virus in an immunosuppressed child post cord blood transplant. J Paediatr Child Health 2007;43:713-5.
19. Ota K, Kim V, Lavi S, et al. Vaccine-strain varicella zoster virus causing recurrent herpes zoster in an immunocompetent 2-year-old. The Pediatric infectious disease journal 2008;27:847-8.
20. Chouliaras G, Spoulou V, Quinlivan M, Breuer J, Theodoridou M. Vaccine-associated herpes zoster ophthalmicus [correction of opthalmicus] and encephalitis in an immunocompetent child. Pediatrics 2010;125:e969-72.
21. Iyer S, Mittal MK, Hodinka RL. Herpes zoster and meningitis resulting from reactivation of varicella vaccine virus in an immunocompetent child. Annals of emergency medicine 2009;53:792-5.
22. Levin MJ, Dahl KM, Weinberg A, Giller R, Patel A, Krause PR. Development of resistance to acyclovir during chronic infection with the Oka vaccine strain of varicella-zoster virus, in an immunosuppressed child. J Infect Dis 2003;188:954-9.
23. Levin MJ, DeBiasi RL, Bostik V, Schmid DS. Herpes zoster with skin lesions and meningitis caused by 2 different genotypes of the Oka varicella-zoster virus vaccine. J Infect Dis 2008;198:1444-7.