Epidemiology of herpes simplex virus type 1 infection 10/12/14 12:14

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Epidemiology of herpes simplex virus type 1 infection

Author Section Editor Deputy Editor
Robyn S Klein, MD, PhD Martin S Hirsch, MD Barbara H McGovern, MD

Last literature review version 18.3: Setembro 2010 | This topic last updated: Outubro 1,
2010
INTRODUCTION — Herpes simplex virus type 1 (HSV-1) infections are frequently asymptomatic
but can produce a variety of signs and symptoms. These include oral or perioral lesions, ocular
infections, nongenital skin lesions, genital skin or mucous membrane lesions, and serious systemic
illnesses such as encephalitis and neonatal disease. (See "Clinical manifestations and diagnosis of
herpes simplex virus type 1 infection".)

HSV-1 is transmitted from person-to-person via infected oral secretions during close contact.
Infection occurs worldwide, equally between the sexes, and without seasonal variation. In the
United States, there are estimated to be approximately 500,000 primary infections per annum [1].
The incubation period of oral infections ranges from 1 to 26 days (median 6 to 8 days) and lesions
range from 1 to 8 days in duration [2,3]. While infection is lifelong, it is rarely fatal in the
immunocompetent host, producing either asymptomatic or mild clinical disease.

Herpetic keratitis continues to be the leading cause of blindness in industrialized countries, with the
predominant disease being of the stromal type [4]. Over the past 20 years, the prevalence of the
disease has decreased in most developed countries. (See "Herpes simplex keratitis".)

TRANSMISSION — Contact with herpetic lesions or oral secretions can produce infection with HSV-
1 [2]. The viral titer is 100 to 1000 times greater when lesions are present [3]; as a result,
transmission is much more likely when the patient is symptomatic [2]. Following primary infection,
HSV can also sometimes be recovered from the stool [5].

In various series, HSV was obtained from 81 to 88 percent of vesicles, 34 percent of ulcers or
crusts, and from the saliva in 3.6 to 25 percent of patients with a positive history or serology
[2,6,7].

In one study, 2 to 9 percent of adults and 5 to 8 percent of children were asymptomatic salivary
excretors of HSV-1 [3]. Overall, 0.65 to 15 percent of adults may be excreting HSV-1 (or HSV-2) at
anytime. There does not appear to be a correlation between ocular and oral infection with HSV-1
[8].

Transmission of ocular HSV-1 has also been documented in a case of corneal transplantation into a
HSV-1 seronegative patient with glaucoma [9]. This infection resulted in the loss of sight.

HSV-1 transmission via oral-genital contact has also been recognized as a contributing cause of
increasing cases of HSV-1 genital herpes infection, especially among young adults [10,11].

SEROEPIDEMIOLOGY — Worldwide, more than 90 percent of people are seropositive for HSV-1 by
the fourth decade of life, especially those of lower socioeconomic groups [3]. This pattern was also
present in the United States during the 1940s and 1950s; however, the prevalence rates for people
from industrialized countries and middle class societies have been declining. In a follow-up cross-
sectional seroprevalence survey in the United States, trends in HSV-1 and HSV-2 infections in 1999

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Epidemiology of herpes simplex virus type 1 infection 10/12/14 12:14

to 2004 (11,508 participants) were compared to 1988 to 1994 (9165 participants) [12]. The survey
demonstrated that the seroprevalence of HSV-1 had declined from 62 to 58 percent, a relative
decrease of seven percent [12]. A European study determined a seroprevalence of 65.6 percent
[13]. Subsequent data indicate that seroprevalence for both HSV-1 and HSV-2 in the United States
is decreasing, suggesting that young adults may be at increased risk for primary infections with
these viruses [14].

It is unclear whether the declining rate is secondary to changes in hygiene or to a protective effect
of infection with HSV-2, the prevalence of which has been rising in developed societies [3]. In one
prospective study of new HSV-1 and HSV-2 infections, approximately two-thirds of new HSV-1
infections were symptomatic and genital infections due to HSV-1 were as common as oropharyngeal
infections (0.5 cases per 100 person-years) [15]. Two studies have demonstrated that prior
seropositivity to HSV-1 increased the likelihood of asymptomatic seroconversion for HSV-2 infection
[13,15].

In the United States, seroprevalence has been reexamined using newer type-specific antibody
assays and sera from the National Health and Nutrition Examination Survey [16]. Among African-
American children, more than 35 percent were positive for HSV-1 by the age of five compared to
18 percent in Caucasian children. HSV-1 antibodies remained two times more common in African-
Americans through adolescence but the difference had disappeared by age 40.

For patients with a positive history of cold sores, the rates of seropositivity are higher (93 percent)
[17]. Antibody titers have not been found to correlate with positive cultures or the presence of
lesions [2].

Populations at risk — Cutaneous and ocular HSV-1 infections have been recognized as a health
risk for athletes involved in contact sports and for healthcare workers. One study, for example,
evaluated students at a high school wrestling camp: 34 percent had active herpetic infection [18],
which commonly involved the head (73 percent), extremities (42 percent), and trunk (28 percent).
Interestingly, attack rates for wrestlers were higher for heavyweights compared to lightweights (67
versus 25 percent).

Healthcare workers comprise a second population at risk for infection with HSV-1. One report found
that medical and nursing personnel had a slightly lower prevalence of antibodies to HSV-1 (less
than 50 percent) than the general population (80 to 90 percent), making them particularly
susceptible to primary infection [19]. In addition, HSV-1 is responsible for nosocomial outbreaks in
many hospitals, providing another reason to adopt universal precautions.

In one reported case, a physician developed HSV-1 keratoconjunctivitis after intubating an

immunocompromised patient with pneumonia [20]. The physician had not been wearing eye
protection or gloves during the procedure. In that hospital, nosocomial HSV-1 infection occurred in
9 to 15 of 10,000 hospital admissions per year.

Restriction endonuclease fingerprinting of HSV DNA has been used for contact tracing in nosocomial
outbreaks of HSV. In at least one instance, it revealed that multiple isolates occurred in a "single"
outbreak [21].

There may also be groups at reduced risk. There are, for example, two studies suggesting possible
protection afforded by prior infection with one serotype of HSV on infection with the other. In one
report, pregnant women with no prior infection with HSV had a 3.7 percent chance of
seroconverting to HSV-2 during their pregnancy compared to 1.7 percent in those with prior
exposure to HSV-1 [22]. In another study of Japanese women with genital herpes, isolation of HSV-
1 from the lesions correlated with seronegativity for HSV-2 [23].

Transmission of neonatal HSV-1 generally occurs from nongenital and occasionally nonmaternal

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sources. In one series of six infants diagnosed with HSV-1 infection, only four mothers had past or
current mucocutaneous HSV-1 infection, while all six fathers had positive histories [24]. In one set,
neither parent had active HSV at the time of neonatal infection.

A rapid rise in HSV-1 antibodies occurs during the first five years of life, coincident with a rise in
primary infections [19]. In one report, 20 percent of normal children between the ages of seven
months and two years had HSV in their saliva [5].

HSV-1 RECURRENCE PATTERNS — Recurrent HSV-1 infections of the lips and perioral area are
estimated to occur in 20 to 40 percent of the population worldwide [6]. Among patients with
recurrence, there is substantial variability in the frequency with which this occurs, ranging from
once per month in 5 to 23 percent to every one to four months in 58 to 61 percent to twice per
year in 19 to 61 percent [6,25]. No differences between the sexes have been observed.

Recurrent ocular HSV-1 infections are also common. Approximately 25 to 50 percent of patients
with primary herpetic keratitis will have a recurrence within two years [26].

HSV-1 recurs more often in the orolabial region and HSV-2 recurs more often in the genital area
[1,27]. In one study, for example, the mean monthly recurrence rate for orolabial HSV-1 was
twenty-fold higher than for orolabial HSV-2 (0.020 versus 0.001) [27]. In the same report, the rate
of genital HSV-2 recurrences was much higher (0.33 per month).

THE IMMUNOCOMPROMISED HOST — HSV-1 infection in the immunocompromised host causes

more morbidity and mortality than in the general population. This relationship can be illustrated by
the following observations:

In one series, 62 percent of fatalities following renal transplantation were caused by viruses,
with HSV contributing in 60 percent [28]. The incidence of HSV-1 infection after renal
transplantation has ranged from 35 to 85 percent, depending upon the presence and amount
of antibody to HSV and the level of immunosuppression required to prevent graft rejection
[28,29]. Exogenous infection does not appear to be a factor in posttransplant HSV-1
infections.

In an analysis of 40 patients undergoing chemotherapy for a variety of malignancies, the

presence of HSV-1 in oral mucosa, as assessed by PCR, was detected in 70 percent prior to
chemotherapy and 87.5 percent two weeks after initiation of the chemotherapeutic cycle.
While 25 percent of patients manifested oral disease prior to starting chemotherapy, 65.7
percent of patients had oral mucosal changes at the second two-week assessment [30].

In a cohort of bone marrow transplant recipients, 82 percent of seropositive patients

developed reactivation of HSV after transplantation [31]. HSV infection in these patients was
usually secondary to endogenous reactivation rather than primary infection; the presence of
antibody to HSV in the donor did not affect the response of the recipient.

The prevalence of HSV-1 cutaneous infections in HIV-infected patients is in the range of 5 to

20 percent [32]. Lesions tend to be more severe than in immunocompetent hosts,
demonstrating local destruction and persistent shedding of virus. In addition, the incidence of
acyclovir resistance in immunocompromised patients is higher than in the general population.
In contrast to cutaneous infection, the incidence of herpetic keratitis in HIV-infected patients
is similar to that in the HIV-negative population [33].

SUMMARY AND RECOMMENDATIONS

HSV-1 is transmitted from person-to-person via infected oral secretions during close contact.

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Epidemiology of herpes simplex virus type 1 infection 10/12/14 12:14

Infection occurs worldwide, equally between the sexes, and without seasonal variation. (See
'Introduction' above.)

The incubation period of oral infections ranges from 1 to 26 days (median 6 to 8 days) and
lesions range from 1 to 8 days in duration. (See 'Transmission' above.)

Contact with herpetic lesions or oral secretions can produce infection with HSV-1 [2]. The viral
titer is 100 to 1000 times greater when lesions are present; as a result, transmission is much
more likely when the patient is symptomatic. (See 'Transmission' above.)

Worldwide, more than 90 percent of people are seropositive for HSV-1 by the fourth decade
of life, especially those of lower socioeconomic groups. (See 'Seroepidemiology' above.)

Cutaneous and ocular HSV-1 infections have been recognized as a health risk for athletes
involved in contact sports and for healthcare workers. (See 'Populations at risk' above.)

The incidence of acyclovir-resistant HSV is more common in the immunocompromised host

than in the normal host. (See 'The immunocompromised host' above.)

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