Viral load and antibody boosting following herpes zoster diagnosis

Abstract

Background: Acute varicella zoster virus (VZV) replication in shingles is accompanied by VZV antibody boosting. It is unclear whether persisting virus shedding affects antibody levels.

Objectives: To investigate the relationship between VZV viral load and antibody titres in shingles patients during six months following diagnosis and assess whether VZV antibody titre could discriminate patients with recent shingles from healthy population controls.

Study design: A prospective study of 63 patients with active zoster. Blood samples were collected at baseline, one, three and six months to measure VZV DNA and IgG antibody titre. We compared VZV antibody titres of zoster patients and 441 controls.

Results: In acute zoster, viral load was highest at baseline and declined gradually over the following six months. Mean antibody titres rose fourfold, peaking at one month and remaining above baseline levels throughout the study. Antibody levels at one, three and six months after zoster were moderately correlated with baseline but not subsequent viral load. Regarding use of antibody titres to identify recent shingles, to achieve 80% sensitivity, specificity would be 23.4%, 67.7%, 64.8% and 52.6%, at baseline, visit 2, 3 and 4 respectively, whilst to achieve 80% specificity, sensitivity would be 28.3%, 66.1%, 52.6%, 38.6%, at baseline, visit 2, 3 and 4 respectively.

Conclusions: Clinical VZV reactivation boosted VZV antibody levels and the level of boosting was dependent upon baseline viral replication. While antibody titres could discriminate patients with shingles 1-6 months earlier from blood donor controls, there was a large trade-off between sensitivity and specificity.

Keywords: Antibody; Herpes zoster; Varicella zoster virus; Viral load.

Fig. 1

Log VZV viral load and antibody titres over time.

Fig. 2

Association between log viral load and antibody titre, at the same and various time points: Pearson correlation coefficients and coefficients from multivariable linear regression models displayed. Note: Adjusted coefficients represent the effect of a one unit change in the variable value on the log mean antibody titre, adjusted for age, sex, ethnicity and immunosuppression status.

Fig. 3

ROC curve with table showing antibody cut-off values and specificity/sensitivity if test was required to have 80% sensitivity/specificity, at each visit. *If the VZV IgG antibody titre value is greater than or equal to the cut-off, then the individual is declared positive (affected) by this cut-off approach, else negative (healthy), and these are compared to the actual status to determine sensitivity and specificity.