1. Journal of Infectious Diseases Advance Access published October 16, 2013
EDITORIAL COMMENTARY
The Scarlet H
David W. Kimberlin
Department of Pediatrics, University of Alabama at Birmingham
Keywords.
herpes simplex virus type 1; herpes simplex virus type 2; HSV; genital herpes; neonatal herpes.
On 2 August 1982, TIME magazine published a cover story titled “The New
Scarlet Letter,” with the word “Herpes”
emblazoned in blood-red font above a
picture of a young couple. The article effectively described the silent epidemic of
genital herpes, providing a warning siren
to alert millions of Americans of a significant risk associated with the sexual revolution of the 1960s and 1970s. It was a
great example of investigative journalism
at its best. And then . . . nothing. To my
knowledge, herpes has not appeared on a
cover of any of the major news magazines
since. To understand why, one need look
no further than the letters H.I.V. The
destinies of human immunodeficiency
virus (HIV) and herpes simplex virus
(HSV) have been inextricably linked.
This is true at the biologic level, where
the genital ulcerative disease caused by
HSV type 2 (HSV-2) enhances HIV
transmission [1]. It also is true at the interface of health and the public, where
the (legitimately) scary prospects of the
global HIV epidemic rapidly overtook
Received and accepted 23 July 2013.
Correspondence: David W. Kimberlin, MD, Division of Pediatric Infectious Diseases, University of Alabama at Birmingham, 1600 7th Ave S, CHB 303, Birmingham, AL 35233
(dkimberlin@peds.uab.edu).
The Journal of Infectious Diseases
© The Author 2013. Published by Oxford University Press
on behalf of the Infectious Diseases Society of America. All
rights reserved. For Permissions, please e-mail: journals.
permissions@oup.com.
DOI: 10.1093/infdis/jit459
public awareness of virtually all other infectious diseases during the 1980s. As the
scientific community, and eventually the
American public, came to recognize the
manner by which HIV is spread, terms
such as “safe sex” entered the public
lexicon. The success of public campaigns
to educate the citizens of the world and,
thereby, limit the spread of HIV are irrefutable. As with all good things, though,
there have been unintended consequences. One of these has been the embrace of
the notion that oral sex is “safe” because
it does not involve penile-vaginal or
penile-anal penetration. Although oral
sex is safer in the sense that it cannot
result in an unintended pregnancy, it
nevertheless carries its own significant
risk of transmission of sexually transmitted infections, including transmission of
HSV type 1 (HSV-1) from the mouth to
genital mucosa.
Against this backdrop, Bradley and
colleagues, in this issue of the Journal of
Infectious Diseases, have produced yet
another remarkable study in the longrunning series of National Health and
NutritionExaminationSurvey(NHANES)
publications. Dating back almost 50 years,
the National Center for Health Statistics
(NCHS) has used these serial surveys to
describe the health and nutritional status
of adults and children in the United
States. Beginning in the mid-1970s,
NHANES specimens have been evaluated
for HSV-1 and HSV-2 seroprevalence.
Previous NHANES publications have
documented the increase in HSV-2 seroprevalence among adolescents and adults
of childbearing age during the early and
mid-1980s [2, 3]. Indeed, NHANES data
substantially drove the budding awareness of genital herpes that culminated in
the TIME cover story in 1982. The article
by Bradley et al [4] continues in the outstanding tradition of NHANES HSV
publications. Their key finding is that
HSV-1 seroprevalence among 14- to 19year-olds has declined by nearly 23%
from 1999–2004 to 2005–2010, from
39.0% to 30.1% for an absolute difference
of about 9% [4]. Stated differently, almost
1 in 10 adolescents who 10 years ago
already would have acquired HSV-1 earlier in life now are vulnerable to getting
a primary infection as they enter their
sexually active years. This is occurring at
the same time in which sexual practices
have substantially shifted, with increases
in oral sex reported in adults over the
past 20 years [5–7]. In 2007–2010, almost
half of 15- to 19-year-olds and more than
four-fifths of 20- to 24-year-olds had
engaged in oral sex practices [8]. This
produces the perfect storm of serosusceptible adolescents engaging in sexual
behavior that increases the likelihood
that their first exposure to HSV-1 will be
on their genitalia, and, thus, that they
will develop HSV-1 genital herpes. Increasing rates of genital HSV-1 infection
already are being seen in several studies
published over the past decade [9–11],
and Bradley and colleagues’ data give
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2. reason to be concerned that this trend
will accelerate.
Why should we care? It appears that
HSV-1 is less likely than HSV-2 to reactivate in the genital tract of men and nonpregnant women [12]. Additionally, most
genital HSV shedding occurs from reactivation of viral infection, rather than from
primary HSV disease [13–15]. Thus, it is
possible that genital herpes could actually
decline over the longer time period if a
larger proportion of primary genital
herpes infections are due to the serotype
that is less likely to reactivate and result
in clinically apparent or inapparent recurrent viral shedding. However, this
possibility of fewer recurrent genital HSV
infections years down the road is dwarfed
by the current risk of an explosion in
genital HSV-1 primary infections as serosusceptible adolescents engage in oral
sex practices that expose them to HSV-1
for the first time on their genitalia. This
is likely, as 50%–60% of Americans in
their 20s and 30s currently are infected
with HSV-1 [4], with the overwhelming
majority of them having oral infection
that they acquired earlier in their lives.
We saw an epidemic of genital herpes
caused by HSV-2 in the 1980s when
15%–20% of the population had HSV-2
infections. Imagine the consequences
with >50% of the population intermittently shedding virus orally and also
engaging in oral sex practices with seronegative partners.
The most serious consequence of
genital herpes is transmission of HSV to
an infant at the time of delivery [16].
Both HSV-1 and HSV-2 can be of devastating consequence to neonates, because
they lack a mature immune system to
battle the virus [17]. Up to 30% of infected infants will die from this infection if
they have the most severe form of the
disease (disseminated disease) [18]. Among
infants with central nervous system
disease, approximately 30% will be left
with lifelong neurologic sequelae from
their neonatal brain infections, even with
optimal therapy [19]. The infants at
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highest risk of acquiring neonatal herpes
are those born to women with firstepisode primary infections, with almost
60% of them developing neonatal disease
if exposed to the virus at delivery as they
pass through an infected birth canal [15].
These infants also are the ones who are
more likely to develop disseminated neonatal HSV disease, as they lack the protection of maternal antibodies passed
across the placenta [20]. If we begin to see
more primary (and possibly even recurrent [21]) genital HSV-1 infections,
especially among young women acquiring
it as they emerge from adolescence, it
is logical to hypothesize that we will see
neonatal herpes more frequently over
the next decade, and that it will be more
severe.
It is ironic that the destinies of HSV
and HIV remain so intertwined in the
United States. Three decades ago, HIV
displaced HSV-2 as the principal virus
competing for the attention of the public
health community at a time when public
awareness of genital herpes was just beginning to rise. Furthermore, the “safe sex”
educational advances that have contributed significantly to limiting the spread of
HIV since then have contributed to modifications in sexual practices that now are
poised to contribute to a resurgence in
genital herpes, although this time with
HSV-1. As a result, today we find ourselves once again confronting a scarlet
letter, and the lives of many infants yet to
be born may hang in the balance.
Notes
Financial support. This work was supported
under contract with the Virology Branch, Division
of Microbiology and Infectious Diseases of the
National Institute of Allergy and Infectious Diseases (HHSN272201100034C, HHSN272201100035C,
HHSN272201100037C, HHSN272201100038C,
N01-AI-30025).
Potential conflicts of interest. Author certifies 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.
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