Although rates of herpes zoster (HZ) recurrence are low—estimates range from 0.5% during 10 years of follow-up to 6.4% during 6.5 years of follow-up—it has been unclear whether the second episode is caused by the same varicella-zoster virus (VZV) strain as the first.

Now, a new study published in Vaccine offers an answer to that question while also illuminating other issues about shingles that recurs.

Researchers from the Veterans Affairs San Diego Healthcare System and the University of California San Diego took a close look at the Shingles Prevention Study (SPS), a large efficacy trial of live attenuated Oka/Merck zoster vaccine (ZVL). They found that assay-confirmed second episodes of HZ occurred in two of 660 placebo and one of 321 ZVL recipients during a mean follow-up of 3.13 years. An additional two ZVL recipients experienced a second episode of HZ in the Long-Term Persistence Substudy. 

All episodes of HZ were caused by wild-type VZV, they write, with the first and second episodes of HZ occurring in different dermatomes in each of the five participants and contralateral recurrences in two. Time between the first and second episodes ranged from 12 to 28 months, according to the study.

The study team used VZV DNA isolated from rash lesions from the first and second episodes of HZ to sequence the full-length VZV genomes. “Our analysis and comparison of the VZV genomes from the first and second episodes of HZ in each of the five participants indicate that both episodes were caused by the same VZV strain,” the authors note. “This is consistent with the extraordinary stability of VZV during the replication phase of varicella and the subsequent establishment of latency in sensory ganglia throughout the body. Our observations also indicate that VZV is stable during the persistence of latency and the subsequent reactivation and replication that results in HZ.”

The article also points out that the risk of HZ recurrence has been generally reported to be greater in females than in males, adding that this review, although not statistically significant, had consistent results. “In addition, while all four females in our study were immunocompetent throughout, the only male with a recurrence was immunocompromised when he experienced both episodes of HZ,” the authors write.

Despite previous studies suggesting that HZ-associated pain was significantly less severe in second than in first episodes, this study found higher severity-of-illness scores in all but one of the second episodes, “suggesting that a first episode of HZ may not mitigate the pain associated with a second episode.”

The researchers also suggest that the ZVL is not preventive for recurrence, explaining, “Although our numbers are small, ZVL does not appear to protect against HZ recurrence; in the SPS, HZ recurrence rates were the same in vaccine and placebo recipients. This is not surprising since any residual difference in VZV-CMI between ZVL and placebo recipients would likely have been eliminated by the VZV-CMI response to their first episode of HZ.”
The study emphasizes that no case of HZ during the SPS and its substudies was caused by ZVL. “This suggests that establishment of latency by the Oka vaccine strain of VZV is rare in immunocompetent older individuals who are already latently infected with wild-type VZV when vaccinated,” the authors write.

The SPS, a randomized, double-blind, efficacy trial, was conducted between November 1998 and April 2004 and enrolled 38,546 immunocompetent participants aged ≥60 years for a mean of 3.13 years after receiving ZVL or placebo.

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