Impact of Varicella Vaccine on Varicella-Zoster Virus Dynamics

Abstract

SUMMARY 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.

Trends in varicella mortality in the United States: Data from vital statistics and the national surveillance system

“…19 In addition, foreign-born adults should be assessed for evidence of immunity and receive 2 doses of varicella vaccine if they lack evidence of immunity. The epidemiology of varicella in other countries, especially tropical countries, differs in that foreign-born adults may still be susceptible to varicella in adulthood, 23 when varicella is more severe. State health departments should continue to report varicella-related deaths to CDC using the CDC death www.taylorandfrancis.cominvestigation worksheet (http://www.cdc.gov/vaccines/pubs/ surv-manual/appx/appendix 19-2-varicella-wrsh.pdf).…”

“…However, currently commercially available laboratory tools cannot differentiate varicella from herpes zoster. VZV Immunoglobulin (Ig) G avidity can help distinguish between cases of varicella and herpes zoster with a low avidity confirming primary VZV infection, 23 the assay is not widely available and cannot distinguish varicella from herpes zoster among vaccinated persons.…”

Varicella and herpes zoster vaccine development: lessons learned

“…Derived from wild type VZV isolated from a child with typical varicella, vOka was produced through serial passage of the wild-type virus in human embryo fibroblast cells and guinea pig embryo fibroblasts with additional propagation in human diploid cells (WI-38) [1,39]. The vOka is attenuated for replication in skin but less so in other target tissues such as T cells and trigeminal ganglia [40,41].…”

“…However, in vitro studies of a VZV latency model using induced pluripotent stem cell neurons show that, while both vOka and wild-type VZV are equally capable of establishing latency, vOka is less able to reactivate [67]. This is supported by studies among both immunocompetent and immunocompromised individuals, which show significantly lower rates of zoster among vaccinated children than among those infected naturally with wild-type virus [1,68]. …”

“…Along with herpes simplex virus types 1 and 2, VZV is part of the alpha herpesvirus family of DNA viruses. Its linear 125-kb double-stranded DNA genome encodes at least 71 unique open-reading frames (ORFs) [1], with approximately 40 conserved genes shared with other human herpesviruses [2]. The genome is located within an icosahedral capsid, surrounded by a protein tegument and encapsulated by a polyamine, lipid, and glycoprotein envelope [3].…”