E D I T O R I A L C O M M E N TA R Y
An Evolving Understanding of Genital Herpes Pathogenesis:
Is It Time for Our Approach to Therapy to Change
As Well?
Edward W. Hook III
University of Alabama at Birmingham and Jefferson County Department of Health, Birmingham, Alabama
(See the article by Tata et al, on pages 499–504.)
In this issue of the Journal, Tata and co-
workers present data from a small, inten-
sively studied group of women with gen-
ital herpes due to herpes simplex virus
(HSV) type 2, demonstrating that during
a 30-day period these women experienced
both symptomatic and asymptomatic gen-
ital viral shedding bilaterally and at areas
innervated by dorsal root nerve ganglia on
both sides of the midline [1]. These find-
ings challenge widely held beliefs that gen-
ital HSV infection resides in solitary or
adjacent dorsal root ganglia on just one
side of the body, suggesting that the in-
fection may occur on both sides of the
midline and in more ganglia than previ-
ously thought. Although the data need to
be validated by additional investigations,
they encourage conceptualization of gen-
ital herpes as a chronic, nearly continu-
ously active infection rather than an in-
Received 4 November 2009; accepted 4 November 2009;
electronically published 20 January 2010.
Potential conflicts of interest: E.W.H. has received honoraria
and research funding from GlaxoSmithKline, Becton Dickinson,
and Merck.
Financial support: GlaxoSmithKline, Becton Dickinson, and
Merck.
Reprints or correspondence: Dr Hook, University of Alabama
at Birmingham, 703 19th St S, ZRB 242, Birmingham, AL 35294-
0007 (ehook@uab.edu).
The Journal of Infectious Diseases 2010; 201:486–7
 2010 by the Infectious Diseases Society of America. All
rights reserved.
0022-1899/2010/20104-0002$15.00
DOI: 10.1086/650303
486 • JID 2010:201 (15 February) • EDITORIAL COMMENTARY
fection characterized by periodic recur-
rences interspersed with periods of disease
inactivity. Tata et al studied a small num-
ber of patients and did not include any
men; moreover, as they acknowledge, 3 of
their 4 patients had become infected
within the preceding year and were thus
were in a period of infection when both
recurrences and asymptomatic viral shed-
ding are more frequent than in persons
with older infections. Nonetheless, the
data are of great potential importance, be-
cause they further challenge widely held
beliefs regarding genital herpes and, by ex-
tension, its management. They also sug-
gest that it is time to use these sorts of
data to guide the evolution of our ap-
proach to genital herpes management and
prevention.
Thirty years ago there were no easily
taken, highly effective medications for
genital herpes treatment and no reliable
serological tests to help diagnose infection
with the virus. In 1982, herpes was char-
acterized as “Today’s Scarlet Letter” in a
cover story in Time magazine [2]. Much
has changed since that time. We now
know that about 1 in 5 American adults
has genital herpes but that only ∼10% of
them are aware of their infection [3, 4].
We know that “classic herpes” is not typ-
ical herpes and that in many persons with
genital herpes the manifestations of initial
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and recurrent genital infections are subtle,
varied, and frequently overlooked [5].
Furthermore, we have learned that the vast
majority of HSV transmission occur
through contact with sexual partners who
are unaware of their infections and are
asymptomatic when the infection is trans-
mitted [6, 7].
Our tools for herpes diagnosis and
management have evolved as well. Type-
specific serological tests can now provide
reliable information about the presence or
absence of infection [8, 9], and polymerase
chain reaction testing has both substan-
tially increased the sensitivity of tests for
the virus and simplified specimen acqui-
sition and transport [10]. There are also
multiple highly effective antiviral thera-
peutic agents that not only are proved to
accelerate lesion healing and reduce the
discomfort associated with symptomatic
recurrence of infection but that also, when
taken continuously as suppressive therapy,
reduce asymptomatic shedding of the vi-
rus and have been proved in a rigorously
conducted clinical trial to significantly re-
duce transmission of infection between
sexual partners [7, 11]
For most clinicians however, the ap-
proach to therapy has not kept pace with
our evolving understanding of this wide-
spread infection. All too many clinicians
treat most patients with newly diagnosed
herpes with episodic therapy directed at
managing the signs and symptoms of pe-
riodic symptomatic recurrences. The data
presented by Tata et al [1] add to the ar-
gument, from a patient and public health
perspective, that a national campaign for
serological testing of those at risk would
provide the foundation for more effec-
tive efforts to control HSV transmission
to others, and that suppressive therapy
should be the preferred approach for most
sexually active persons with HSV-2 whose
sex partners are not known to be infected.
This would not be a simple task. Clinicians
would need to reconceptualize their ap-
proach to diagnosis and management. In
addition, there would be a need to portray
genital herpes not as a “scarlet letter” but
rather as a widespread untoward conse-
quence of human sexuality, the impact of
which on personal and public health could
be reduced through broader testing and
more aggressive treatment. That is where
the data take us; when will we act?
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