Tuesday, March 18, 2008

Cell-Mediated Immune (CMI) Responses and Zoster-associated Pain in Herpes Zoster (HZ) Patients

M. J. Levin1, S. K. Tyring2, J. Xu3, W. W. B. Wang3, P. M. Keller3, J. G. Smith3, M. J. Caulfield3, J. L. Barben3, J. E. Stek3, S. Senior3, F. P. Schodel3, I. S. F. Chan3, K. Schlienger3, and J. L. Silber3. (1) University of Colorado Health Sciences Center, Denver, CO, USA, (2) University of Texas Health Sciences Center, Houston, TX, USA, (3) Merck & Co., Inc, North Wales, PA, USA

Learning Objectives for this Presentation:
By end of presentation participants will be able to:
1. Discuss VZV-specific CMI responses.

Varicella-zoster virus (VZV)-specific CMI responses were compared over time following an episode of HZ and in age-matched controls without HZ.

Discuss VZV-specific CMI responses.

Multicenter study evaluated variability & kinetics of VZV-specific CMI responses in adults with acute (<=2 hr after lesion onset) HZ or w/in 4-6 days after lesion onset & in age-, race-, & gender-matched healthy controls (HC) using validated IFN-gamma ELISPOT assay. PCR verified VZV among suspected cases. Blood drawn for immunogenicity in HZ patients at Day 0, 2 wks, 6 wks, & 6 mos. Zoster brief pain inventory (validated questionnaire) assessed zoster-associated pain.

HZ patients (n=140) had significantly higher IFN-gamma ELISPOT responses to VZV than did HC (n=140).
ELISPOT geometric mean count (GMC) responses (95% CI) <=2-hrs:
HZ Patients >=60 yrs: Day 0, n=49, GMC=110 (60,201); Week 2, n=48, GMC=235 (155,357)
HZ Patients 21-59 yrs: Day 0, n=23, GMC=111 (54,227); Week 2, n=21, GMC=198 (122,322)
HC >=60 yrs: Day 0, n=50, GMC=19 (12,30); Week 2, n=45, GMC=18 (9,34)
HC 21-59 yrs: Day 0, n=28, GMC=59 (31,112); Week 2, n=18, GMC=56 (25,127)
Mean pain score (95% CI) across age groups at 1 wk post-rash (n=106) was 6.0 (5.5, 6.5) & at 2 wks post-rash (n=119) was 3.5 (2.9, 4.0). Percent HZ patients with substantial pain (score>=3) at 6 wks post-rash increased with age from 8% (21-49 yrs), to 16% (50-59 yrs), to 22% (>=60 yrs).

VZV-specific CMI response substantially boosted by episode of HZ, measured by ELISPOT. Older adults had lower VZV-specific CMI than younger subjects at baseline, but boosting effect of HZ was substantial for all age groups. HZ patients experienced considerable zoster-associated acute (1-2 wks post-rash) pain across age groups, while chronic pain increased with age.ased with age.