The first known description of herpes simplex virus (HSV) dates from more than 4,500 years ago, when Hippocrates used the term herpes to refer to lesions that seemed to creep or crawl along the skin. However, it wasn’t until the early 20th century that scientists confirmed the infectious nature of the virus, and it wasn’t until the 1970s that the health care community recognized HSV as an STD with devastating consequences.¹

Today the dangers are increasingly well-known. Genital herpes has emerged as a major risk factor in the spread of HIV, the virus that causes AIDS. Recent studies suggest that an estimated 19% of sexually transmitted HIV infections in the U.S. and 47% of sexually transmitted HIV infections in sub-Saharan Africa can be attributed to infections with genital herpes.²

Nurses as educators can make patients and the public aware of the danger herpes presents and ensure that they understand strategies for prevention or management with  antiviral oral medications.

HSVs are DNA-containing, enveloped viruses that cause incurable, recurrent, life-long latent infections in their human hosts. The viruses are endemic worldwide, and approximately 90% to 95% of humans become infected with HSV during their life spans.³ Two strains of HSV exist: HSV-1 and HSV-2.

Traditionally, HSV-1 has been responsible for approximately 80% of herpes virus infections above the waist (e.g., herpetic lesions of the lips, face, and mouth) and 20% of genital infections. The reverse has been true for HSV-2, which causes 80% of herpes virus infections below the waist (e.g., herpes genitalis) and 20% of oral infections.⁴ However, today the traditional HSV-1/HSV-2 ratio seems to be changing in younger age groups in women. Several recent studies in the U.S. show that HSV-1 (oral herpes) may be responsible for up to 40% of genital herpes among the younger population.³

Where HSV thrives

HSV-1 and HSV-2 are fragile viruses in that they require a lipid coating (envelope) that needs to remain moist for them to attach and to penetrate a host cell.³ When the viruses are exposed to the air, the lipid envelopes dry and fall apart, and the viruses become noninfectious. This means that for HSV transmission to occur, body fluid containing the virus from an infected person excreting HSV must be deposited directly onto susceptible tissues (e.g., oral, ocular, genital, or anal mucosa) of an uninfected person. (Therefore, a toilet seat cannot be the source of genital herpes).

Once the herpes virus comes into contact with susceptible tissue, it begins to replicate in the epithelial cells around the contact site (skin or mucous membrane), producing a characteristic vesicle on an erythematous base. It then enters the nerve endings in the skin under the entry site and travels along the sensory nerve fibers to the dorsal root ganglia, where it becomes latent (inactive).

Oral herpes establishes latency in the trigeminal ganglia under the skull in front of each ear and recurs in sites innervated by the trigeminal nerve (eyes, nose, and mouth). Genital herpes becomes latent in the sacral nerve root ganglia at the base of the spine (S2-S5) and recurs in the genital area.⁵ A variety of stimuli — such as fever, trauma, sunlight, emotional stress, immunosuppression, and menstruation — can trigger reactivation. Once reactivated, the virus travels from the ganglia back down along the sensory nerves to the site of initial outbreak, where it replicates and induces an active or subclinical infection.^3,5

Herpes infection may be first-episode primary infection, which is HSV in a person without antibodies to either HSV-1 or HSV-2. Herpes infections can also be first-episode nonprimary infections, which is HSV-2 in a person with prior HSV-1 antibodies or HSV-1 in a person with prior HSV-2 antibodies. First-episode nonprimary infections tend to be less severe than primary infections.

The cold sore story

Primary HSV-1 infections (first-episode — no HSV-1 or HSV-2 antibodies) are usually acquired during childhood (aged 6 months to 5 years) from contact with oral secretions containing the virus. The typical “cold sore” or “fever blister” appears three to 12 days after exposure as clusters of painful blisters (vesicles) on an erythematous base.⁶ Vesicles typically appear around the lips or nose although they can occur anywhere on the pharyngeal and oral mucosa, including the tongue, buccal mucosa (the mucous membrane lining of the inner cheek), palate, and floor of the mouth. After a vesicular stage of less than 48 hours, the vesicles rupture and coalesce, forming a large, painful, ulcerative lesion covered with crusts. Ten to 14 days later, the lesions will reepithelialize and heal without scarring.

Maximum viral shedding occurs during the acute outbreak. However, viral shedding from the saliva may continue for three weeks or more.^5,7 A number of systemic symptoms including fever, headache, foul breath, myalgias, cervical lymphadenopathy, and pain can be associated with first-episode primary HSV-1.^3,6

After the primary infection, 20% to 40% of people with oral herpes experience recurrences. Lesions can recur one to 12 times per year and are often triggered by stress. Before recurrence and the development of vesicles, there is usually a prodrome (symptoms that occur before an outbreak) of pain, burning, itching, or tingling that can last from six to 53 hours. Systemic symptoms are not usually associated with recurrences.⁶

Genital infections

Most genital herpes infections in the U.S. are caused by HSV-2. More than 50 million people are infected, and an estimated 1.6 million new cases occur each year.^2,8 Based on nationwide surveys in the last two decades, 20% to 30% of people aged 15 to 29 and 35% to 60% of people aged 60 are infected with HSV-2.⁷ The cumulative lifetime incidence for infection with the virus is 25% for white women, 20% for white men, 80% for African-American women, 60% for African-American men, and 22% for Hispanics.⁷ As can be seen by these percentages, more women are infected with HSV-2 than men. In addition, women also have more severe disease, physical symptoms, and complications.^3,8 The variation in infection rates among racial groups is due to differences in poverty levels, access to care, sexual and health-related behavior, and the use of illicit drugs.⁷ The HSV-2 infection rates may not give a complete picture of genital herpes since up to 40% of infections may now be caused by HSV-1.

The primary infection with genital herpes typically occurs two to 12 days after exposure with a prodrome of pain, tingling, and burning, which may last up to 24 hours. During the first episode, patients can develop flulike symptoms accompanied by severe burning pain, erythema, multiple vesicles, pustules, and ulcers of the genitalia. Dysuria, profuse vaginal or urethral discharge, and tender inguinal lymphadenopathy are common.⁸ The ulcerative lesions, in both men and women, can persist for as long as six weeks until crusting and reepithelialization occur.^3,8

In women, herpetic lesions commonly appear on the vulva, around the vaginal opening, and in the vagina, cervix, and perineum. Vesicles can also appear on the buttocks and thighs.⁵ In 10% to 20% of infections, lesions develop in the urethra, where they can cause painful urination and urinary retention. In addition, up to 36% of women will develop aseptic meningitis as a complication of the initial infection.^3,5

In men, the herpetic lesions are not as extensive. They appear on the shaft or glans of the penis and sometimes on the scrotum, thighs, and buttocks. Thirty to 40% develop urethritis with severe dysuria and mucoid discharge,⁵ and aseptic meningitis occurs in 12% of cases.³

During the first year after the primary infection with HSV-2, up to 90% of patients have one or more recurrent outbreaks of genital herpes (the median rate is four), 38% have more than six, and 20% have more than 10.^5,8 Patients who had long-lasting primary infections (i.e., 35 days or more) experience recurrent infections twice as often as those with shorter-lasting primary infections, and men are 20% more likely to develop recurrences than women.^4,8 

Most recurrent outbreaks are milder than the primary disease. The recurrent prodromal symptoms — ranging from mild tingling to stabs of pain in the buttocks, legs, and hips³ — can last from two hours to two days.⁵ However, fewer lesions develop, and viral shedding occurs at lower concentrations and for a shorter time, about three days.⁸

The majority of people (50% to 70%) with genital herpes (HSV-2) have unrecognized symptomatic or asymptomatic disease.^3,8 Nevertheless, in more than 95% of infected people, reactivation, replication, and shedding of the virus occur regardless of whether clinical symptoms are present.⁹ For instance, in healthy immunocompetent men, asymptomatic shedding from mucocutaneous surfaces or genital secretions occurs on approximately 10% to 15% of days, and in healthy women on 20% to 25% of days.⁹ For both men and women, asymptomatic shedding with HSV-2 occurs 10 times more often than with HSV-1.³

The majority of people with genital herpes do not experience clinically apparent outbreaks. Seventy percent of people who become infected with genital herpes acquire the infection from asymptomatic sex partners who do not realize that they are infected and shedding the virus.^2,8

The HIV connection

Recently, infection with genital herpes (HSV-2) has been recognized as a major risk factor for sexual acquisition and transmission of HIV infection. Studies show that the risk of acquiring HIV infection increases two to four times for people infected with genital herpes.⁹ In addition, the per contact risk of acquiring HIV from an HIV-infected sex partner is five times greater for HSV-2 infected people.² The increased risk for acquiring HIV is thought to be the result of four biological mechanisms:

1. Mucosal disruptions caused by genital lesions/ulcers during symptomatic episodes or microlesions that occur during asymptomatic recurrences provide a direct portal for HIV entry.
2. Herpetic ulcerations bring about an influx of activated HIV target cells (CD4+ lymphocytes and macrophages) to the genital tract for HIV attachment and entry. (The CD4 lymphocyte is the target cell that HIV needs to carry out its infectious invasion of the human host.)
3. A coinfection with HIV increases the frequency of HSV-2 reactivation and the duration of HSV-2 shedding.
4. In turn, increased frequency of HSV-2 reactivation and the duration of HSV-2 shedding are associated with an increase in HIV replication on mucosal surfaces and an increase in the plasma HIV viral load during HSV-2 reactivations.⁹

Currently, there are only two strategies for a sexually active infected person to follow to prevent HSV-2 transmission: taking daily antiviral therapy and using condoms. Daily antiviral therapy can reduce the frequency of HSV-2 reactivations and the amount of HSV-2 on genital mucosal surfaces.²

Male condoms or other barrier protection can significantly reduce HSV-2 transmission rates from an infected male partner to a susceptible woman since the penile skin is the most common site of HSV-2 shedding. However, condoms apparently do not offer males as much protection. The reason may be that infected women shed the virus from the skin around the genital area, and a male condom does not offer susceptible men protection against contact with those skin areas.⁹

Control, not cure

No cure exists for HSV. However, several antiviral oral medications reduce the severity and duration of infection, and rates of recurrence. The approved oral treatments include acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir hydrochloride (Valtrex). These drugs have comparable clinical outcomes and can be used for episodic treatment or long-term suppressive therapy.

Episodic treatment is best for patients who have infrequent recurrences. These patients should receive a prescription for the medication so that therapy can be started as early as possible after the onset of symptoms (i.e., during the prodrome or when vesicles first appear). Suppressive therapy is recommended for patients with more than six recurrences per year. Daily suppressive antiviral treatment can reduce the frequency of recurrences and viral shedding by 70% to 80%. The safety of long-term therapy has been well documented, and treatment is not associated with significant adverse effects.⁸

Other HSV infections

Aseptic meningitis caused by HSV is an inflammation of the membranes that line the brain and spinal cord. It can occur three to 12 days after the onset of genital lesions (HSV-2). Women are at greater risk than men,⁵ and symptoms include headache, fever, stiff neck, and photophobia. Most cases resolve in two to seven days without complications.⁵

Herpetic whitlow is an intensely painful infection of the fingers that can result from autoinoculation or other direct contact between the HSV and a break in the skin, usually a torn cuticle. The infection is common in health care workers and is usually caused by unprotected exposure to oral and genital secretions when caring for patients. Two to 20 days after exposure to the virus, the infected finger becomes red and swollen; and over seven to 10 days, groups of small clear-yellowish or pus-filled vesicles appear. Ten to 14 days later, the vesicles ulcerate, and the lesions crust over and heal. At this point, viral shedding ends. The herpes whitlow infection recurs in up to 50% of patients.¹⁰

One of the most devastating consequences of genital herpes (HSV-1 or HSV-2) is the transmission of infection to the newborn. Neonatal herpes, which affects about 1,500 to 2,000 neonates a year, is associated with extremely high morbidity and mortality.¹¹

Up to 50% of babies born to women who acquire a primary HSV infection during the third trimester of pregnancy are likely to become infected at delivery through contact with the virus in the maternal genital tract.⁷ For women infected with HSV before the third trimester, the risk of transmission of HSV during recurrent outbreaks of the virus is much lower, between 1% and 5%, because of the protective effects of maternally transferred antibodies.¹¹ The overall risk of HSV neonatal infection from a woman with a history of genital infection is extremely low, estimated to be fewer than three infections in 10,000 births.¹¹

Education for prevention

Nurses can play a significant role in the prevention and control of HSV through patient counseling and education. Patients should be told that although there is no cure for HSV infection, medication will help relieve symptoms and reduce viral shedding. They should be educated to recognize prodromal symptoms so antiviral treatment can be started before lesions appear.

In addition, nurses can caution patients to practice abstinence when prodromal symptoms or lesions are present and explain that a risk of transmission exists during these periods as well as during asymptomatic periods. Patients should be advised to always use condoms with susceptible partners because of the possibility of asymptomatic viral shedding. Patients should also be encouraged to inform their sex partners that they have genital herpes.

Health care workers with oral herpes infections should be cautioned to avoid contact with immunocompromised people and neonates while lesions are present. Health care workers with herpetic whitlow infections should be excluded from contact with patients until their lesions have crusted.¹²

Millions of people throughout the world are living with HSV infections, and while no cure exists, education and antiviral treatment can greatly improve their quality of life.