Herpes: No simple(x) answer
|Old treatments and new drugs in development can ease or prevent, but still not cure, this viral disease.
On the bulletin board of the website Herpes.com, a resource for people suffering from oral and genital herpes, a 24-year-old woman writes: I found out I had herpes when I was 3 months pregnant with my first child. I contracted [it] from my husband and was depressed for weeks. I have since been divorced. It is very difficult for me to have a relationship with a man because I have to go into detail about this disease. Most men are scared after that.
Another visitor to the site, a 30-year-old man, writes, My entire family has herpes. Since we are a close family and kiss each other a lot, we were all infected with oral herpes and have recurrent outbreaks, a few times a year. I was amazed reading of peoples traumatic reaction to having herpes. It is an inconvenience for me, nothing more.
Although both visitors have herpes, their experiences are vastly different. The first visitor has genital herpes, a sexually transmitted disease that is often socially devastating. The second visitor has oral herpes, an infection of the mucous membranes of the mouth that arises as a seemingly innocuous fever blister. Both illnesses stem from infection by one of two different viruses, herpes simplex type I (HSV-1) and herpes simplex type II (HSV-2), and it is impossible to tell which virus a victim is carrying. Although oral herpes is usually caused by HSV-1 and genital herpes is most often caused by HSV-2, both viruses can infect either site.
When residing in its site of preference, HSV-2 can change the course of marriages and devastate relationships. However, it rarely causes serious health problems. HSV-1, on the other hand, can in rare cases cause blindness, encephalitis, and even death. Both viruses are spreading in epidemic proportions, infecting millions of people worldwide every year. In the United States, an estimated 1 in 5 people over the age of 12 is infected with genital herpes, and nearly 4 out of 5 adults contract oral herpes by the time they reach age 50. Yet, because most infected individuals do not show symptomsand those who do are often uninformed about transmissiontypes I and II continue to spread at alarming rates.
Old standby treatments, promising new drugs, and the possibility of a future vaccine have bolstered the hopes of physicians and researchers to treat or at least prevent both infectionsbut knowledge remains the most powerful weapon to keep these incurable viral diseases in check.
Most individuals with oral herpes contract it as children through a social kiss, but genital herpes is a sexually transmitted disease, usually passed on in adulthood through unprotected intercourse or oral sex. Most oral herpes cases are caused by HSV-1, and the majority of genital herpes cases are caused by HSV-2.
According to Hilary E. Baldwin, vice chairwoman of the department of dermatology and associate professor of clinical dermatology at the State University of New York Health Science Center in Brooklyn, NY, the route of entry for both viruses is a cut, however small, in the skin of the recipient. Although the virus cannot penetrate the tough, keratinized cells of the skins outer layer, it slips in through a break in the skin to invade the more vulnerable cells of the dermis. After entering a dermis cell, the virus turns it into its personal replicating factory.
For the next several days, each infected cell churns out millions of viruses. The cells become so full that they eventually rupture, releasing more viruses to infect surrounding cells.
Within two weeks of exposure, some infected individuals have their first outbreak, which can appear as a painful lesion the size of a quarter to a half-dollar or as a small red and swollen patch. It might be full of tiny blisters, craters, or crusts. A herpes infection can manifest in many ways, but the most common symptom, says Baldwin, is nothing at all. The vast majority, a full two-thirds of infected individuals, never show symptoms.
After the symptoms, if any, fade away, the virus retreats to the safety of neural ganglia. For oral herpes, the virus takes up residence in the trigeminal ganglion, a collection of nerve cells near the ear. In genital herpes, it sets up camp in the sacral ganglion at the base of the spine. There, either virus stays dormant until a weakened immune system allows it to flare up again in the skin.
Between outbreaks, infected individuals show no signs of illness. However, even when an infected person is asymptomatic, he or she can pass on oral or genital herpes through viral shedding, an insidious release of infectious viral particles from the affected site. Researchers believe that viral shedding from individuals showing no symptoms of disease causes the vast majority of new herpes infections.
Its one of the reasons why we have an epidemic now, says Baldwin.
Acyclovir, famciclovir, and valaciclovir are antiviral medications currently used for HSV-1 and HSV-2 infections. These drugs are approved for both preventive and episodic treatment. Taken daily, they can prevent outbreaks or, at the very least, lessen their severity. When taken only at the onset of symptoms, they merely shorten the duration of an outbreak and reduce viral shedding. They cannot stop an outbreak once symptoms have started and do not prevent the spread of disease.
All three medications work by the same mechanism: inhibiting viral DMA polymerase, an essential enzyme needed for the herpes virus to replicate. Each is equally effective at preventing and treating outbreaks. However, because all of them must travel through the bloodstream, these drugs cannot wipe out the infection at its source. Because no blood vessels pass through the spinal or trigeminal ganglia, the only time the medications can attack the virus is when it is headed back toward the skin, which is infused by blood vessels, to cause another outbreak.
The idea is to have the medication on board at the moment that the first virus reaches the skin, so that it wont replicate into a million viruses that then create a lesion. You have to catch it, says Baldwin. [The drugs] work better preventatively than they do for treatment, because the medication cant get to the infected areas.
Although both HSV-1 and HSV-2 prefer to use thymidine kinase to replicate, sometimes, cautions Baldwin, herpes viruses mutate to become resistant to these inhibitors. Recently, two companies announced new drugs now in development that aim to inhibit a different enzyme also needed for the virus to replicate, known as helicaseprimase inhibitors.
The drugs, Bayer AGs BAY 57-1293 and Boehringer Ingelheims BILS 179 BS, are administered in a pill form and have shown impressive effects, according to a commentary in the April 2002 issue of Nature Medicine. They appear to keep the virus in check in mice and guinea pigs, and both compounds will go into clinical trials with humans as the next step toward approval.
This summer, a new candidate for a herpes vaccine goes into Phase III clinical trials. Known as Hervac for the trial and developed by GlaxoSmithKline, the vaccines active agent is a purified glycoprotein from HSV-2s outer coat.
According to Joel Ward, professor of pediatrics at the University of California, Los Angeles (UCLA), and director of the UCLA Center for Vaccine Research, one of the principal investigational sites for the vaccine project, the vaccine has shown promise for use in women but not in men. Although researchers are at a loss to explain the disparity, the health benefits are still extremely significant.
Until a viable vaccine is developed, the only prevention methods available include avoiding kissing and sharing food and utensils for oral herpes, and abstinence or using latex barriers during oral sex and intercourse for genital herpes. However, many of those who posted their experiences on the Herpes.com website expressed an abiding sense of optimism that a cure will be developed soon. A 22-year-old man writes, Theyll have a vaccine or a cure developed soon. With the Human Genome Project opening up possibilities every day, its almost ridiculous to assume herpes will be an issue in 25 years.
American Social Health Association; www.shastd.org.
Herpes.com, a resource of Global Health Services, Inc.; www.herpes.com.
Herpes Help, a resource of GlaxoSmithKline; www.herpeshelp.com.
Christen L. Brownlee is an associate editor of Modern Drug Discovery. Send your comments or questions regarding this article to email@example.com or the Editorial Office by fax at 202-776-8166 or by post at 1155 16th Street, NW; Washington, DC 20036.
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