Advances in the understanding of the pathogenesis and epidemiology of herpes zoster

Abstract

The primary varicella zoster virus (VZV) infection results in chickenpox (varicella), which is transmitted via the airborne route. VZV is highly infectious, but in the USA the incidence of varicella has been reduced by 76-87% as a result of the varicella vaccine. The virus establishes latency in the dorsal root ganglia during varicella and, when reactivated, travels along the sensory nerve axons to cause shingles (herpes zoster [HZ]). There are over 1 million cases of HZ in the USA each year, with an estimated lifetime attack rate of 30%. The incidence of HZ, which causes significant morbidity, increases with age and reaches approximately 10 cases per 1,000 patient-years by age 80. Cell-mediated immunity (CMI) is known to decline with age as part of immunosenescence, and decreased CMI is associated with reactivation of VZV. This article provides an overview of our emerging understanding of the epidemiology and pathogenesis of varicella and HZ, in addition to exploring the current theories on latency and reactivation. Understanding the risk factors for developing HZ and the complications associated with infection, particularly in older people, is important for prompt diagnosis and management of HZ in primary care, and they are therefore also reviewed.

Fig. 1

Varicella and HZ cases reported to the Royal College of General Practitioners, England and Wales, 1967–92. Reproduced with permission from Miller E, Marshall R, and Vurdien J. Epidemiology, outcome and control of varicella-zoster infection. Rev Med Microbiol 1993;4:222–230.

Fig. 2

The incidence of HZ increases with age. Figure adapted from Edmunds et al, 2001 and Gauthier et al, 2009.^, Abbreviations: MSGP4, Fourth Morbidity Survey in General Practice; RCGP, Royal College of General Practitioners.

Fig. 3

Phylogeny of VZV.^– Figure adapted from Loparev et al, 2007.

Fig. 4

Intercellular spread of VZV. Numbers indicate the steps in synthesis of VZV in the basal epidermis (no release of infectious VZV) and the superficial epidermis (release of infectious VZV). Figure courtesy of Gershon A and Gershon M.

Fig. 5

VZV-specific CMI declines with age.

Fig. 6

Prevalence of PHN according to age. Reproduced from Kost RG, Straus SE. Postherpetic neuralgia-pathogenesis, treatment, and prevention. N Engl J Med 1996 Jul 4;335(1):32–42. © 1996 Massachusetts Medical Society. All rights reserved.