Effect of viral load on the outcome of herpes zoster

Abstract

Varicella-zoster virus (VZV) is a member of the Herpesviridae family, primary infection with which causes varicella, more commonly known as chicken pox. Characteristic of members of the alphaherpesvirus subfamily, VZV is neurotropic and establishes latency in sensory neurons. Reactivation of VZV causes herpes zoster, also known as shingles. The most frequent complication following zoster is chronic and often debilitating pain called postherpetic neuralgia (PHN), which can last for months after the disappearance of a rash. During episodes of acute zoster, VZV viremia occurs in some, but not all, patients; however, the effect of the viral load on the disease outcome is not known. Here we describe the development of a highly specific, sensitive, and reproducible real-time PCR assay to investigate the factors that may contribute to the presence and levels of baseline viremia in patients with zoster and to determine the relationship between viremia and the development and persistence of PHN. VZV DNA was detected in the peripheral blood mononuclear cells (PBMCs) of 78% of patients with acute zoster and in 9% of healthy asymptomatic blood donors. The presence of VZV in the PBMCs of patients with acute zoster was independently associated with age and being on antivirals but not with gender, immune status, extent of rash, the age of the rash at the time of blood sampling, having a history of prodromal pain, or the extent of acute pain. Prodromal pain was significantly associated with higher baseline viral loads. Viral load levels were not associated with the development or persistence of PHN at 6, 12, or 26 weeks.

FIG. 1.

Standard curve generated by real-time PCR. Serial dilutions of each viral plasmid standard (•), ranging from 8 to 8 × 10⁷ copies per reaction mixture, were used to generate the standard curve. The C_T values that corresponded to the PCR cycle number were plotted against the copy number of each viral standard. The slope of the line was −3.57, the y intercept was 40.2, and the correlation coefficient was 99.7%.

FIG. 2.

Distribution of VZV viral loads among 130 patients with zoster and 53 asymptomatic blood donors. Bars with horizontal stripes, asymptomatic blood donors; bars with gray blocks, represent zoster patients.