Do Vaccines Cause Disseminated Varicella Infection?

Updated November 8, 2023



Disseminated varicella infection is a serious potential complication of natural infection with varicella virus, particularly among immunodeficient persons. Thus, varicella vaccine prevents disseminated varicella infection by protecting against natural infection. However, varicella vaccines can rarely cause disseminated varicella infection in patients with severe immune deficiency, for whom the vaccine is contraindicated. Other vaccines currently routinely recommended to the general population in the U.S.* do not cause disseminated varicella infection.

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 disseminated varicella infection 1; however, it did not provide convincing evidence due to a lack of validity and precision 2.

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 disseminated varicella infection after varicella vaccination 3-22, and concluded that these cases together presented strong mechanistic evidence supporting an association 2. In immunodeficient persons, disseminated varicella infection can also result in pneumonia 3-5,14-16, meningitis 7, or hepatitis 3-5,9,11.

There have been several deaths due to disseminated varicella in children who had undiagnosed severe combined immunodeficiency (SCID) at the time of vaccination. However, it is extremely rare for children with SCID to remain undiagnosed at the age of varicella vaccination 23-26.

* These conclusions do not necessarily consider vaccines recommended only for special populations in the United States such as Yellow Fever vaccine (international travelers) or Smallpox vaccine (military personnel), or vaccines no longer recommended to the public such as the Janssen (J&J) COVID-19 vaccine.


1.         Black S, Shinefield H, Ray P, Lewis E, Hansen J, Schwalbe J, Coplan P, Sharrar R, Guess H. Postmarketing evaluation of the safety and effectiveness of varicella vaccine. The Pediatric infectious disease journal 1999; 18(12): 1041-6.

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.         Galea SA, Sweet A, Beninger P, Steinberg SP, Larussa PS, Gershon AA, Sharrar RG. The safety profile of varicella vaccine: a 10-year review. J Infect Dis 2008; 197 Suppl 2: S165-9.

4.         Sharrar RG, LaRussa P, Galea SA, Steinberg SP, Sweet AR, Keatley RM, Wells ME, Stephenson WP, Gershon AA. The postmarketing safety profile of varicella vaccine. Vaccine 2000; 19(7-8): 916-23.

5.         Wise RP, Salive ME, Braun MM, Mootrey GT, Seward JF, Rider LG, Krause PR. Postlicensure safety surveillance for varicella vaccine. Jama 2000; 284(10): 1271-9.

6.         Angelini P, Kavadas F, Sharma N, Richardson SE, Tipples G, Roifman C, Dror Y, Nofech-Mozes Y. Aplastic anemia following varicella vaccine. The Pediatric infectious disease journal 2009; 28(8): 746-8.

7.         Bryan CJ, Prichard MN, Daily S, Jefferson G, Hartline C, Cassady KA, Hilliard L, Shimamura M. Acyclovir-resistant chronic verrucous vaccine strain varicella in a patient with neuroblastoma. The Pediatric infectious disease journal 2008; 27(10): 946-8.

8.         Chaves SS, Haber P, Walton K, Wise RP, Izurieta HS, Schmid DS, Seward JF. 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.

9.         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(8): 764-6.

10.       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(36): 5878-82.

11.       Ihara T, Kamiya H, Torigoe S, Sakurai M, Takahashi M. Viremic phase in a leukemic child after live varicella vaccination. Pediatrics 1992; 89(1): 147-9.

12.       Jean-Philippe P, Freedman A, Chang MW, Steinberg SP, Gershon AA, LaRussa PS, Borkowsky W. Severe varicella caused by varicella-vaccine strain in a child with significant T-cell dysfunction. Pediatrics 2007; 120(5): e1345-9.

13.       Kraft JN, Shaw JC. Varicella infection caused by Oka strain vaccine in a heart transplant recipient. Arch Dermatol 2006; 142(7): 943-5.

14.       Kramer JM, LaRussa P, Tsai WC, Carney P, Leber SM, Gahagan S, Steinberg S, Blackwood RA. Disseminated vaccine strain varicella as the acquired immunodeficiency syndrome-defining illness in a previously undiagnosed child. Pediatrics 2001; 108(2): E39.

15.       Levy O, Orange JS, Hibberd P, Steinberg S, LaRussa P, Weinberg A, Wilson SB, Shaulov A, Fleisher G, Geha RS, Bonilla FA, Exley M. 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(7): 948-53.

16.       Waters V, Peterson KS, LaRussa P. Live viral vaccines in a DiGeorge syndrome patient. Arch Dis Child 2007; 92(6): 519-20.

17.       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(10): 713-5.

18.       Ota K, Kim V, Lavi S, Ford-Jones EL, Tipples G, Scolnik D, Tellier R. Vaccine-strain varicella zoster virus causing recurrent herpes zoster in an immunocompetent 2-year-old. The Pediatric infectious disease journal 2008; 27(9): 847-8.

19.       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(4): e969-72.

20.       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(6): 792-5.

21.       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(7): 954-9.

22.       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(10): 1444-7.

23.       Leung J, Siegel S, Jones JF, Schulte C, Blog D, Schmid DS, Bialek SR, Marin M. Fatal varicella due to the vaccine-strain varicella-zoster virus. Human vaccines & immunotherapeutics 2014; 10(1): 146-9.

24.       Schrauder A, Henke-Gendo C, Seidemann K, Sasse M, Cario G, Moericke A, Schrappe M, Heim A, Wessel A. Varicella vaccination in a child with acute lymphoblastic leukaemia. Lancet (London, England) 2007; 369(9568): 1232.

25.       Woo EJ. Letter to the editor: Fatal varicella due to the vaccine-strain varicella-zoster virus. Human vaccines & immunotherapeutics 2015; 11(3): 679.

26.       Dutmer CM, Asturias EJ, Smith C, Dishop MK, Schmid DS, Bellini WJ, Tirosh I, Lee YN, Notarangelo LD, Gelfand EW. Late Onset Hypomorphic RAG2 Deficiency Presentation with Fatal Vaccine-Strain VZV Infection. Journal of clinical immunology 2015; 35(8): 754-60.