A 28-year-old stockbroker takes his first true vacation in over five years, spending two full weeks at a ski resort in Colorado. During his stay at the resort, he meets and becomes intimately involved with an attractive 25-year-old woman. They engage in vaginal intercourse several times and agree to keep in touch after returning to their respective hometowns and jobs. A few days after returning to his office, the stockbroker develops painful, itchy sores on the shaft of his penis. He also experiences low grade fever, headache, malaise, myalgias, and some inguinal lymphadenopathy. He is so busy at his office (a real workaholic) that he is determined not to seek medical help unless his condition becomes overtly dangerous. As a matter of fact, his symptoms clear up after two weeks or so and the man starts to feel far better. However, he has some awareness of sexually transmitted diseases and is a bit worried about what happened because he realizes that it might be connected to his behavior at the ski resort. During a rather difficult phone call to the young women with whom he was intimate, he learns that she has had past episodes of genital herpes and experienced an outbreak of active lesions herself right after returning from the ski resort.

Question 7.1: What is the most likely causative agent?

Considering the woman's history and their recent intimate behavior, the most likely cause is herpes simplex virus type 2 (HSV-2), which generally causes infections below the waist. However, HSV-1, which is most often associated with oral infections such as cold sores, sometimes causes genital infections as well (about 10% of the cases in the U.S.).

Question 7.2: What may happen if the man fails to seek treatment?

In all probability, the stockbroker will experience recurrences of the lesions. The disappearance of the symptoms associated with the initial infection does not mean that the virus was eliminated from his body. Rather, it has merely stopped replicating rapidly in the epithelial cells and has infected the innervating neurons in the genital area. In the neurons, HSV enters a condition called latency, in which the viral genome is maintained inside of the host cell but normal replication of the virus is repressed. Latency probably occurs because only a limited number of viral encoded proteins are transcribed. However, the viral genome may later become activated (reactivation), resulting in normal viral gene expression, replication, and release of new infectious virions. The release of viruses from the neuron and their subsequent infection of epithelial cells lead to extensive replication of the virus, damage to epithelial tissues, and reappearance of the painful lesions. The cycle of latency and reactivation can continue throughout an infected person's lifetime, with the virus never being eliminated from the body.

The stockbroker in this case is likely to experience a recurrence of symptoms on an average of 3 to 4 times per year for many years if he fails to seek treatment. (The actual number and frequency of recurrences varies widely from one victim to another.) During this initial case, his genital lesions and other symptoms persisted for two weeks because the immune response takes time to evolve. Nevertheless, immune responses are activated during the initial incident and, as a result, the recurrences probably will be briefer and milder, lasting an average of 7-10 days instead of 2-3 weeks. Unfortunately, the immune responses in most individuals are not adequate to fully prevent the recurrences.

Question 7.3: What causes recurrences of this disease?

The full range of factors that may reactivate HSV and cause a recurrence of the lesions is not yet known. Factors that have been cited frequently as stimuli for reactivation include stress, trauma, fever, and excessive exposure to sunlight.

Question 7.4: Is there a cure for this disease?

Genital herpes can be treated with various drugs. Acyclovir ointment (Zovirax), applied directly to the lesions, is useful for treating a first clinical episode of genital herpes. Relatively severe infections can be treated with IV or oral acyclovir for 7 10 days. Valcyclovir (Valtrex) is also used for an initial episode of genital herpes. However, these drugs cannot eliminate the virus from an infected individual. They merely inhibit active replication of the virus, thereby forcing the virus back into the latent phase and keeping it there as long as the therapy is continued. This clears up active lesions and helps to prevent their recurrence, but it does not permanently cure the disease.

Question 7.5: What other infections can this agent cause?

Herpes simplex viruses can cause lytic infections of many different types of human cells. In the head and neck area, they cause cold sores and fever blisters (mostly HSV-1), gingivostomatitis, pharyngitis, and keratitis (usually limited to one eye). Herpes whitlow, an infection of the finger, and herpes gladiatorum, an infection of the body, occur when the virus enters through abrasions or cuts in the skin. Herpes encephalitis is usually caused by HSV-1, whereas HSV meningitis is most often a complication of genital HSV-2 infection. Infections of the visceral organs are possible as well. HSV infection in neonates, typically acquired in the birth canal during delivery, is a devastating and usually fatal disease that is caused by HSV-2 and that involves dissemination to the liver, lung, and other organs.

Question 7.6: How is this disease transmitted?

Genital herpes is transmitted by direct person-to-person contact, during sexual intercourse. The risk of transmission is highest when the "donor" partner has an active case (i.e., lesions are present), but the disease can also be transmitted during latency because infected individuals tend to shed virions at the infected mucosal surfaces. Shedding rates are highest during the initial years of acquisition and decrease over time. Shedding rates also tend to increase a few days prior to a recurrence (i.e., prior to the appearance of lesions), so an asymptomatic individual may be particularly infectious during that period. Transmission by asymptomatic individuals makes control and prevention of genital herpes difficult.

Question 7.7: How prevalent is this disease?

Approximately 47 million North Americans are believed to be infected with genital herpes and there are about 500,000 new cases each year in the U.S. First visits to physicians for genital infections increased 7-fold between 1966 and 1989. The annual cost of this disease in the U.S. is estimated to be about $100 million.