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Thursday, December 6, 2012

Genital herpes virus reactivates widely throughout genital tract

ScienceDaily (Jan. 30, 2010) — Genital herpes caused by a reactivation of herpes simplex virus type 2 (HSV-2) is generally treated as a lesion in one specific area of the genital region. A new study, however, finds that the virus can frequently reactivate throughout the genital tract, an important new concept that could help guide both HSV-2 treatment and prevention. Now available online, the study appears in the Feb. 15 issue of The Journal of Infectious Diseases.

In the study, Christine Johnston, MD, MPH, and colleagues at the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle collected daily samples during a 30-day period from seven separate genital sites in four women infected with HSV-2. HSV-2 was detected from more than one anatomic site on 56 percent of days when there was viral shedding -- and on genital surfaces on both sides of the participants' bodies on most days when virus was detected at more than one site.

Using a detailed sampling method and a sensitive assay, the authors showed that both symptomatic and asymptomatic HSV-2 reactivations often occurred at widely spaced regions throughout the genital tract. These reactivations were often on both sides of the body, even though clinical lesions typically emanate from one anatomic spot. The study's findings illustrate an important new concept in HSV-2 pathogenesis, the authors wrote, and may help in developing comprehensive treatment that both suppresses and limits the transmission of HSV-2 infection.

The authors also noted limitations of their study, including a small sample size and the unique features of the study's subjects. For example, all participants had a history of symptomatic genital herpes, and three of the four had acquired HSV-2 infection within the past year, increasing the chances of high viral reactivation and lesion rates. Additionally, although there were a high proportion of days with lesions during the study period, two of the participants who had recently acquired genital herpes contributed the majority of lesion days.

In an accompanying editorial, Edward W. Hook III, MD, of the University of Alabama at Birmingham, called the study's findings "of great potential importance, as they further challenge widely held beliefs regarding genital herpes and, by extension, its management." Many clinicians treat patients with newly diagnosed herpes episodically, managing the signs and symptoms of periodic symptomatic recurrences, Dr. Hook wrote. "From a personal and public health perspective, the biology of the infection suggests that a national campaign for serological testing of those at risk would provide the foundation for more effective efforts to control HSV transmission to others, and that for most sexually active persons with HSV-2 whose sex partners are not known to also be infected, suppressive therapy should be the preferred approach."

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Compound discovered that boosts effect of vaccines against HIV and flu

ScienceDaily (Aug. 26, 2012) — Oxford University scientists have discovered a compound that greatly boosts the effect of vaccines against viruses like flu, HIV and herpes in mice.

An 'adjuvant' is a substance added to a vaccine to enhance the immune response and offer better protection against infection.

The Oxford University team, along with Swedish and US colleagues, have shown that a type of polymer called polyethyleneimine (PEI) is a potent adjuvant for test vaccines against HIV, flu and herpes when given in mice.

The researchers were part-funded by the UK Medical Research Council and report their findings in the journal Nature Biotechnology.

Mice given a single dose of a flu vaccine including PEI via a nasal droplet were completely protected against a lethal dose of flu. This was a marked improvement over mice given the flu vaccine without an adjuvant or in formulations with other adjuvants.

The Oxford researchers now intend to test the PEI adjuvant in ferrets, a better animal model for studying flu. They also want to understand how long the protection lasts for. It is likely to be a couple of years before a flu vaccine using the adjuvant could be tested in clinical trials in humans, the researchers say.

'Gaining complete protection against flu from just one immunisation is pretty unheard of, even in a study in mice,' says Professor Quentin Sattentau of the Dunn School of Pathology at Oxford University, who led the work. 'This gives us confidence that PEI has the potential to be a potent adjuvant for vaccines against viruses like flu or HIV, though there are many steps ahead if it is ever to be used in humans.'

HIV, flu and herpes are some of the most difficult targets to develop vaccines against. HIV and flu viruses are able to change and evolve to escape immune responses stimulated by vaccines. There aren't any effective vaccines against HIV and herpes as yet, and the flu vaccine needs reformulating each year and doesn't offer complete protection to everyone who receives it. Finding better adjuvants could help in developing more effective vaccines against these diseases.

Most vaccines include an adjuvant. The main ingredient of the vaccine -- whether it is a dead or disabled pathogen, or just a part of the virus or bacteria causing the disease -- primes the body's immune system so it knows what to attack in case of infection. But the adjuvant is needed as well to stimulate this process.

While the need for adjuvants in vaccines has been recognised for nearly 100 years, the way adjuvants work has only recently been understood. The result has been that only a small set of adjuvants is used in current vaccines, often for historical reasons.

The most common adjuvant by far is alum, an aluminium-containing compound that has been given in many different vaccines worldwide for decades. However, alum is not the most potent adjuvant for many vaccine designs.

'There is a need to develop new adjuvants to get the most appropriate immune response from vaccines,' says Professor Sattentau, who is also a James Martin Senior Fellow at the Oxford Martin School, University of Oxford.

The Oxford University team found that PEI, a standard polymer often used in genetic and cell biology, has strong adjuvant activity.

When included in a vaccine with a protein from HIV, flu or herpes virus, mice subsequently mounted a strong immune response against that virus. The immune response was stronger than with other adjuvants that are currently being investigated.

The team also showed that PEI is a potent adjuvant in rabbits, showing the effect is not just specific to mice and could be general.

Another potential advantage of PEI is that it works well as an adjuvant for 'mucosal vaccines'. These vaccines are taken up the nose or in the mouth and absorbed through the mucus-lined tissues there, getting rid of any pain and anxiety from a needle. Mucosal vaccines may also be better in some ways as mucosal tissues are the sites of infection for these diseases (airways for respiratory diseases, genital mucosa for HIV and herpes).

Professor Sattentau suggests that: 'In the best of all possible worlds, you could imagine people would have one dose of flu vaccine that they'd just sniff up their nose or put under their tongue. And that would be it: no injections and they'd be protected from flu for a number of years.

'It's just a vision for the future at the moment, but this promising adjuvant suggests it is a vision that is at least possible.'

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The above story is reprinted from materials provided by University of Oxford, via EurekAlert!, a service of AAAS.

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Shingles Raises Risk Of Stroke By 30 Percent Or More In Adults, Study Finds

ScienceDaily (Oct. 9, 2009) — Adults with shingles were about 30 percent more likely to have a stroke during a one-year follow-up than adults without shingles, in a study reported in Stroke: Journal of the American Heart Association.

The risk was even greater when the infection involved the eyes.

Shingles, also called herpes zoster, is a painful skin rash caused by the varicella zoster virus (VZV). VZV is the same virus that causes chickenpox. After a person recovers from chickenpox, the virus stays in the body. Usually the virus doesn’t cause problems, but it can reappear years later, causing shingles.

Shingles is not caused by the same virus that causes genital herpes, a sexually transmitted disease.

“Many studies have shown that people with herpes zoster infection are more likely to develop stroke. But ours is the first to demonstrate the actual risk of stroke following herpes zoster infection,” said Jiunn-Horng Kang, M.D., M.Sc., lead author of the study and attending physician in the Department of Physical Medicine and Rehabilitation and chair of the Sleep Physiological Lab at Taipei Medical University Hospital.

Kang and his associates studied 7,760 patients 18 years and older who received shingles treatment between 1997 and 2001. These people were matched by age and gender with 23,280 adults who weren’t treated for shingles (controls). Their average age was 47.

During the one-year follow-up, 133 shingles patients (about 1.7 percent) and 306 of the controls (about 1.3 percent) had strokes. After adjusting for general factors for stroke risk, the researchers found:

People treated for a shingles infection were 31 percent more likely to have a stroke, compared with patients without a shingles infection.Patients with shingles infections that involved the skin around the eye and the eye itself (herpes zoster ophthalmicus) were 4.28 times more likely to have a stroke than patients without shingles. When the researchers analyzed the risk of stroke by stroke type, they found:Shingles patients were 31 percent more likely to develop an ischemic stroke during the one-year follow-up than those without shingles.The risk of hemorrhagic (bleeding) stroke was 2.79 times higher for people with shingles infection than for people without shingles.

Ischemic strokes, which are caused by the blockage of an artery, account for 87 percent of the new or recurrent strokes that strike about 780,000 Americans annually, according to the American Heart Association.

“Herpes zoster infection is very easy to diagnose, and antiviral medication can be used to treat the infection in the early stages,” Kang said. “While the mechanism by which shingles increases stroke risk remains unclear, the possibility of developing a stroke after a shingles attack should not be overlooked.

Doctors and patients must pay extra attention to controlling other risk factors for stroke, such as high blood pressure, smoking and diabetes.”

Shingles usually starts as a rash on one side of the face or body. The rash starts as blisters that scab after three to five days and usually clears within two to four weeks. There is often pain, itching or tingling in the area where the rash develops.

Researchers didn’t design the study to determine how shingles infection raises stroke risk. But other research suggests that as the herpes zoster virus replicates and attacks the vessel wall, the vessel wall becomes damaged and inflamed. This in turn can cause the vessel to close up, or occlude, blocking blood flow to the brain. Shingles is also the only recognized human virus able to invade cerebral arteries.

In addition, shingles is also associated with severe pain, and the stress of that chronic pain may raise the risk of cardiovascular disease theoretically, Kang said.

Co-authors are Jau-Der Ho, M.D., Ph.D.; Yi-Hua Chen, Ph.D.; and Herng-Ching Lin, Ph.D. Individual author disclosures are on the manuscript.

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Tuesday, December 4, 2012

Herpes medication does not reduce risk of HIV transmission, study finds

ScienceDaily (Jan. 25, 2010) — A five-year international multi-center clinical trial has found that acyclovir, a drug widely used as a safe and effective treatment taken twice daily to suppress herpes simplex virus-2 (HSV-2), which is the most common cause of genital herpes, does not reduce the risk of HIV transmission when taken by people infected with both HIV and HSV-2.

The results of the study are published in the New England Journal of Medicine.

Up to 90% of people with HIV infection also have HSV-2 infection. Most people who are infected with HSV-2 do not know they have the virus because symptoms can be mild or absent. HSV-2 infection can cause recurrent sores and breaks in the skin of the genital region, which can be mild and often go unnoticed. HSV-2 infection also attracts immune cells called CD4 T-cells to the genital region, which HIV uses to establish or pass infection.

Multiple studies have shown that frequent genital herpes recurrences increase the amount of HIV in the blood and genital tract. The HIV virus is also shed from genital herpes ulcers and persons with such ulcers transmit HIV to others more efficiently. Five preliminary studies showed that it is possible to decrease the amount of HIV in the blood and genital tract through treatment to suppress HSV-2, but these studies did not measure whether this translated into a reduction in HIV transmission. Researchers had hoped that acyclovir's ability to suppress the herpes virus, which causes symptomatic genital sores and breaks in the skin but also frequently is active without symptoms, could reduce the likelihood of sexual transmission of HIV from a person with HIV and HSV-2. The study is the first to determine whether twice daily use of acyclovir by individuals who are infected with both HSV-2 and HIV reduced the transmission of HIV to their sexual partners. The authors conclude that daily acyclovir therapy did not reduce the risk of transmission of HIV, in spite of the fact that acyclovir reduced plasma HIV RNA by a ¼ log and the occurrence of genital ulcers due to HSV-2 by 73%.

Led by the University of Washington in Seattle and funded by the Bill & Melinda Gates Foundation, the Partners in Prevention HSV/HIV Transmission Study was conducted among 3,408 African HIV serodiscordant couples, in which one partner had HIV and the other did not. In all the couples, the partner who had HIV also had HSV-2 infection. The study took place at 14 sites in seven countries in eastern and southern Africa (Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda and Zambia). In sub-Saharan Africa, the majority of new HIV infections occur among heterosexual HIV discordant couples, many of whom are in stable partnerships and unaware that one partner has HIV and the other does not. Genital herpes is thought to be a factor in a substantial proportion of new HIV infections in Africa.

The study began recruitment in Nov. 2004 and ended follow-up of participants in Oct. 2008. Results were first announced in May 2009 and were presented at the International AIDS Society (IAS) meeting in Cape Town, South Africa, on July 22, 2009.

In the primary analysis of HIV transmissions determined by laboratory testing to have occurred within the couple and not acquired from an outside partner, there were 41 infections in the acyclovir arm and 43 in the placebo arm -- not a significant difference. Of the partners who were infected with HIV, 68 % were women. Acyclovir suppressive treatment did show significant reductions in the frequency of genital ulcers (by 73%) and the average amount of HIV in the blood (by 0.25 log10 copies/milliliter, a reduction of 40%), compared to the placebo arm.

"As is often the case with large efficacy trials, you learn to expect surprises," said Dr. Connie Celum, the leader of the study and a UW professor of Global Health and Medicine in the Division of Allergy and Infectious Diseases. "We found that, in spite of a significant reduction in plasma HIV levels and genital ulcer disease with acyclovir suppressive therapy, there was no reduction in HIV transmission. This was a disappointing finding, but a critical outcome of this study is the understanding that interventions must achieve a bigger reduction in HIV levels in order to reduce HIV transmission, especially among persons with high HIV levels. This will be important in informing future interventions to reduce HIV infectiousness."

Celum said the study is a direct assessment of the impact of herpes suppression on HIV transmission and is the most direct way to see if it's possible to make a person less infectious and less likely to transmit HIV to their partner. Although the primary outcome of reducing HIV transmission was not observed, Celum said the study achieved many significant mile¬stones that will help to inform HIV prevention research in a number of ways. Among these were HIV testing of approximately 55,000 couples of unknown HIV serostatus, screening of more than 6,500 HIV serodiscordant couples, and enroll¬ment of 3,408 couples in which the HIV- infected partner was dually infected with HSV-2 and not eligible for antiretroviral therapy, based on national guidelines. Adherence to twice daily acyclovir was high, with 88% of doses dispensed (the drug was not dispensed during pregnancy or if visits were missed), and 96% of dispensed doses taken, as measured by pill counts. Retention of study participants at 24 months of follow-up was 92% for HIV infected partners and 84% for HIV uninfected partners.

The Partners in Prevention HSV/HIV Transmission Study is the first clinical trial to directly test whether suppressing HSV-2 infection in HIV-infected persons could reduce rates of HIV transmission and HIV disease progression. The study was randomized, placebo-controlled and double-blinded, meaning that both participants and the care providers did not know which treatment the participants were receiving. Both the placebo and treatment groups received standard HIV prevention services, which included being supplied with condoms, treated for other sexually transmitted infections, and provided care for HIV infection. All participants received extensive counseling, both individually and as a couple, throughout the study period, on how to reduce the risk of HIV infection.

"This was an ambitious study, and I applaud our collaborators at the University of Washington, the investigators and study teams in Africa, the study participants, and the communities where the study was done, for their dedication over the past five years," Celum said. "We will continue to learn from this study about risk factors for HIV transmission, which will bear fruit for both the HIV prevention and the vaccine fields for years to come."

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The above story is reprinted from materials provided by University of Washington.

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Journal Reference:

Celum C. et al. Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2. New England Journal of Medicine, 2010; DOI: 10.1056/NEJMoa0904849

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STDs, midlife and beyond

Baby boomers, and even their parents and adult children, are experiencing a new type of boom-in acquiring sexually transmitted diseases (STDs). Why are STDs on the rise in the 45+ population, and what should we do about it?

Reasons for the Increase

A growing number of midlife and senior adults are engaging in sexual activity and ignoring the risks of unprotected sex. According to a study reported in U.S. Pharmacist, seniors are one-sixth less likely to use condoms than people in their 20s.

In their defense, seniors grew up when talking about sex was taboo, talking about STDs was even more taboo, and formal sex education-where they would have learned about STDs and how to prevent them-hadn't been "invented." But adults who did have formal sex education have no excuses, except laziness, denial--or skipping class.

Compounding the problem is that a decline in immunity in older people makes them more vulnerable to contracting STDs. Additionally, decreased vaginal lubrication and thinning of the vaginal walls increases the risk of micro-tears in post-menopausal women, and these tears facilitate the transmission of STDs.

The Evidence

Researchers at England's West Midlands Health Protection Agency found between 1996 and 2003, STD rates for Chlamydia, genital herpes, genital warts, gonorrhoea and syphilis more than doubled among people 45+. Males in the 55 to 59 age range were significantly more likely to be affected.

The American Geriatrics Society (AGS) Foundation for Health in Aging reports studies that found the same trend of increasing incidences of other STDs: the human papilloma virus, which causes genital and anal warts and cervical cancer, and the human immune deficiency virus ( HIV), which causes AIDS. The Centers for Disease Control and Prevention reports that adults aged 50+ make up 10 percent of all new AIDS cases.

The implications? Health care providers should talk routinely to their older patients about the dangers of unprotected sex.

What You Need To Know

When having sex with a new partner:
Use a condom. Condoms are the most effective protection against STD transmittal. Use lubricants with the condom to reduce the chance of getting sores or small cuts on the penis or inside the vagina--sores and cuts facilitate STD transmittal.Both you and your partner should be tested for STDs and share your results.If your test results show you're both STD-free you can forego the condom as long as you remain monogamous.
For more information visit Global Action on Aging.

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Monday, December 3, 2012

Herpes healing comes in numbers

Seven years ago, Pam Wisniewski stood in her doctor's office and got some news she thought would ruin her life.

"You have genital herpes," a physician's assistant told her.

Wisniewski started sobbing. "I felt like I was going to be alone for the rest of my life," she said. Her dream of marriage to the perfect man and children faded.

"It was devastation at that point," she said.

Today, Wisniewski is living the dream she thought was lost. She and her husband, Mike, are approaching their one-year anniversary and plan on starting a family soon.

And she's helping others make the same transition.

The 29-year-old UNC Charlotte doctorate student moved to Charlotte, N.C., in 2005 and started a herpes and human papillomavirus, or HPV, support group.

She thought it might end up as "a group of 50 people who went out to a movie now and then," she said. Today, Charlotte H has 1,100 members and keeps growing.

At least 45 million people in the United States have contracted Herpes simplex virus, and most don't know it, according to the federal Centers for Disease Control and Prevention. During an outbreak, patients can experience painful blisters and sometimes flulike symptoms early on.

The virus is transmitted through kissing, oral sex and intercourse. Herpes can even spread when a couple uses a condom because the skin around the protected genital area could be infected.

About 20 million people have HPV, which causes benign warts in men and women and sometimes cervical cancer in women.

For those living with herpes or HPV, healing comes in numbers.

As support groups grow in Charlotte, members are transforming their experiences into lessons for the newly infected or longtime fighters suffering alone. For them, herpes or HPV aren't life-stoppers.

Here are some of their stories.

Carle: The Diagnosis

Carla, who requested her last name not be used, started dating a man she met in a divorce support group after her 10-year marriage ended.

Both had initially tested negative for sexually transmitted infections. But routine tests don't detect herpes unless a blood test is requested. Her partner, who did not have any symptoms, unknowingly gave her herpes even though they were using condoms.

Carla, 36, got tested for herpes when painful genital blisters erupted. The results were negative and she was sent home with a topical cream, but she tested positive after a second outbreak.

"It was a little bit to deal with coming off a marriage," she said.

Dr. Lena White at the Mecklenburg County, N.C., Health Department said a classic blister has a white head with a red halo around it. By the time many patients visit their doctors, the lesion may have subsided.

"Sometimes doctors don't have enough evidence to make the diagnosis," she said. Carla, an active member of the Charlotte-based Carolina H support group that started in March, is now in a long-term relationship. "The group keeps you grounded," she said.

John: Feeling Trapped

John, 40, contracted herpes from his girlfriend, who hid her secret from him. He had a reaction many have when they're diagnosed: He thought he might as well marry her because no one else would want him. John also asked that his last name not be used.

"At that time, not knowing anything or without doing any research, I thought we were the only two within three states to have herpes," he said. In fact, a lot of people who are diagnosed limit their dating to stay within the herpes community.

John joined a support group after ending his relationship. He made friends quickly and is now dating a Carolina H group member.

"There's someone there that you're going to relate to and who can show you the ropes" on navigating a new life, he said.

Strength In Numbers

For members, support groups are a chance for lessons and friendships. Some meetings are more social; others are educational. Charlotte H and Carolina H have scheduled gatherings or activities a few times a month.

"Sometimes we talk about it maybe one percent of the time," said Kirk, a Carolina H leader. "We talk about our group of friends probably two or three times a day."


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Sunday, December 2, 2012

Towson biology professor developing silicone implant to battle herpes

Barry Margulies Barry Margulies uses a pasta maker to manufacture the implants that administer herpes treatment. (Kim Hairston, Baltimore Sun / July 24, 2012)

The space sure looked like a science lab, with beakers full of brightly-hued potions and a dry-erase board covered in graphs and mathematical scrawl. But at the heart of the operation sits a hunk of metal with a hand crank on the side.

"It's a pasta maker," said Barry Margulies, a biology professor who presides over the Towson University lab.

No joke. When it occurred to Margulies' graduate researcher that Williams Sonoma might have the answer to their prayers, it was a major breakthrough for the lab's efforts to treat one of America's most prevalent sexually transmitted diseases.

"I work in herpes," said Margulies, smiling a second later as he realized that sounded funny.

He's a jovial character who talks with his feet propped on his desk and decorates his office with pennants and balls from the Philadelphia teams he has cheered since his youth. A Janis Joplin CD peeks out from beside his keyboard.

Using the pasta maker, Margulies and his students make long strands of rubbery material that look like spaghetti noodles. The "noodles" are made of medical-grade silicone, blended with the drug Denavir.

Margulies said they could be the key to long-term, minimally invasive treatment of herpes simplex viruses type 1 and type 2. Inject one bit of the drugged silicone spaghetti in a strategic location, he explained, and the symptoms of the virus could be neutralized for up to five years.

At Massachusetts Institute of Technology, Margulies studied under Robert Langer, one of the nation's leading experts on time-release medication. As a doctoral student at the Johns Hopkins School of Medicine, he immersed himself in virology. The research insight that changed his career path combined the two experiences.

The idea struck him 20 years ago in graduate school. What if herpes patients didn't have to pop a pill or rub cream on their skin every day? What if the medication could be bound to a substance that would release it into the patient's body gradually?

Langer said the medications weren't good enough at the time, but when Margulies revived the idea more than a decade later, his mentor said it could work. The idea seemed so simple that he couldn't believe no one had tried it.

He has pursued the research since 2005, and his tests have found that in mice, the silicone implants reduce the recurrence of herpes. His lab is working on feline tests with counterparts from the University of California, Davis, and the early results are positive. Margulies has a patent pending on the silicone implants.

He has yet to test the implants on human subjects, and with several important questions — where does the drug go in the body when released and where is the optimal point of injection? — yet to be answered, he's not sure when that will happen. The effort might be out of his hands, licensed to a major drug company, by the time clinical trials begin.

"Sometimes, it's frustrating," he said of the protracted development period. "But I know that our sights are set on helping people."

Margulies has taught at Towson since 2001.

He knows some people might be surprised that a product of MIT and Hopkins is performing serious science at former commuter university with a lab staffed mostly by undergraduates. But he said he loves Towson's emphasis on teaching and on engaging students who are only a few years out of high school.

Shamsuddin Khan, a junior who works in the herpes lab, calls Margulies "fatherly" in the way he nurtures student input and fields endless questions. "If I keep asking something, many things one after another, he never feels tired," Khan said. "He keeps talking, applying many different ways to make lessons easier."

Through his work in the lab, Khan said, he has evolved from a scared novice to a scientist with plans to "do something big for the benefit of mankind."

Some of the key insights in developing the implants, such as the pasta maker revelation, have come from students.

"They think it's funny when I say, 'Your ideas can be as good as mine,'" Margulies said. "But the difference is just experience, and actually, experience can put blinders on you sometimes."

childs.walker@baltsun.com

Herpes facts

Definition: Sexually transmitted disease caused by the herpes simplex viruses type 1 (HSV-1) or type 2 (HSV-2). Most genital herpes is caused by HSV-2.

Prevalence: 1 out of 6 Americans ages 14 to 49 has HSV-2 infection.

Treatment: There is no cure. Sufferers can take antiviral medications to shorten and prevent outbreaks or daily suppressive therapy to help reduce transmission.

Source: Centers for Disease Control and Prevention

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