Unsettled Issues of Zostavax
TO THE EDITOR—The article by Schmader
et al  summarizing a Zostavax trial in
50- to 59-year-old participants raises new
concerns and rekindles others . Zosta-
vax vaccine introduces a new virus which,
like chickenpox, becomes latent in cranial
nerves and autonomic and dorsal root
ganglia . These 2 versions of the same
virus will permanently populate similar
anatomic sites. Moreover, clinical reacti-
vations of both vaccine varicella zoster
virus (VZV) and wild-type VZV continue
to occur [4, 5]. It is unknown to what
extent these reactivations reflect waning
immunity or the appearance of novel viral
subtypes unrecognizable by existing im-
cannot be explained on the basis of im-
munosenescence. More importantly, it is
unknown how these 2 distinct viruses in-
teract over time, particularly in hosts who
later become immunocompromised. Zos-
tavax is contraindicated in most patients
with immunologic impairment and in
persons who previously received Varivax.
Varivax, not Zostavax, but lack of immu-
nity was not an exclusionary criterion in
this trial .
The levels of circulating anti-VZV anti-
bodies and their prevalence are already high
in this population, and the incidence of
herpes zoster (HZ) is lower than in older
age groups. Periodic fluctuations in anti-
VZV antibody levels due to subclinical
reactivations of latent VZV may stimulate
immunologic memory in the absence of
exogenous reexposure. Following natural
infections, antibodies to VZV persist for
long periods, with a half-life of around 50
years .Yet, the durabilityof cell-mediated
immunity is perhaps more crucial . Al-
though HZ may be severe, it is usually a
self-limited, readily recognized, nonfatal
clinical entity that responds to treatment
with available antiviral agents even in seri-
ously immunocompromised hosts.
Unfortunately, the influence of Zosta-
vax on other serious complications of
latent VZV such as meningitis, encephali-
tis, myelitis, angiopathy, and ophthalmo-
adequately evaluated. Headache was the
most frequent serious adverse event but
no information is provided regarding its
etiology . Because this study focused
on shingles, other virus-induced compli-
cations like zoster sine herpete may have
been missed, which is comparable to HZ
and postherpetic neuralgia for establish-
ing vaccine efficacy. The confirmation of
HZ cases centered on detection of VZV
DNA by polymerase
(PCR) in specimens from skin lesions.
On the basis of this test, less than half
(129 of 277) of atypical cases of suspected
HZ were actually confirmed as HZ. One
is left wondering what caused the other
148 cases of suspected HZ. Herpes
simplex DNA by PCR was also performed
but no positive results were reported. Pa-
tients with clinical VZV disease may have
false-negative tests for VZV DNA by PCR
, which would result in an underesti-
mation of HZ cases.
In addition, average follow-up in this
study was only 1.3 years. No Hispanics
were included, and white women, all from
developed nations, were overrepresented.
Long-term follow-up of Zostavax recipi-
ents is prudent and necessary. Further
attenuation of the Oka strain of VZV to
render it incapable of establishing latency
could result in a safer vaccine, particularly
However, in the greater scheme of public
health and cost-effectiveness , Zosta-
vax should remain a low priority.
Potential conflicts of interest.
fies no potential conflicts of interest.
The author has submitted the ICMJE Form
for Disclosure of Potential Conflicts of Interest.
Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
Julio C. Arroyo
Palmetto Health Baptist Hospital, Infectious Disease
Section, Infection Control and Epidemiology,
Columbia, South Carolina
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