Impact of varicella vaccine on varicella-zoster virus dynamics

Abstract

The licensure and recommendation of varicella vaccine in the mid-1990s in the United States have led to dramatic declines in varicella incidence and varicella-related deaths and hospitalizations. Varicella outbreaks remain common and occur increasingly in highly vaccinated populations. Breakthrough varicella in vaccinated individuals is characteristically mild, typically with fewer lesions that frequently do not progress to a vesicular stage. As such, the laboratory diagnosis of varicella has grown increasingly important, particularly in outbreak settings. In this review the impact of varicella vaccine on varicella-zoster virus (VZV) disease, arising complications in the effective diagnosis and monitoring of VZV transmission, and the relative strengths and limitations of currently available laboratory diagnostic techniques are all addressed. Since disease symptoms often resolve in outbreak settings before suitable test specimens can be obtained, the need to develop new diagnostic approaches that rely on alternative patient samples is also discussed.

FIG. 1.

Summary profile of day care and secondary school varicella outbreaks reported in the literature. Column 1, Izurieta et al. (63) (day care); column 2, Galil et al. (42) (day care); column 3, Buchholz et al. (16) (day care); column 4, Galil et al. (43) (day care); column 5, Lopez et al. (84) (elementary school); column 6, Parker et al. (103) (elementary school).

FIG. 2.

(A) Model of the VZV genome illustrating the single-base differences between pOka (parental strain Oka) and vOka (vaccine strain Oka). White triangles, SNP located in noncoding region; black triangles, SNP present uniformly among vaccine strains leading to amino acid substitutions; red triangles, SNP present uniformly among vaccine strains that does not lead to amino acid substitutions; pink triangles, SNP present as a mixed base in vaccine preparations and vaccine-associated SNP that leads to amino acid substitutions; blue triangles, SNP present as a mixed base in vaccine preparation that does not lead to amino acid substitutions. Dark blue ORFs are transcribed from the sense strand; yellow ORFs are transcribed from the antisense strand. (B) Display of VZV genome architecture. TRS, terminal repeat short; TLR, terminal repeat long; UL, unique long; US, unique short; IRL, internal repeat long; IRS, internal repeat short; ori, origin of replication.