Microbicide & Herpes (2)

Genital herpes is one of the most prevalent sexually transmitted infections worldwide and is the most common cause of genital ulcers. Despite increased public awareness and the initiation of efforts to prevent transmission, the prevalence of herpes simplex virus (HSV) type 2 continues to increase.

What makes HSV so difficult to control is that most sexual and perinatal transmission occurs during unrecognized or asymptomatic shedding. The impact of genital herpes as a public health threat is amplified because of its epidemiological synergy with HIV/AIDS. Thus, there is an urgent need for novel prophylactic methods, such as topical microbicides designed for genital application, to prevent both HSV and HIV transmission.

In summary, genital herpes is a critical global health priority because of its devastating impact on young adults and infants and its association with the HIV/AIDS epidemic. Topical microbicides that block transmission at the mucosal surface may provide a realistic method of intervention for worldwide distribution. Currently, there are several candidate drugs being advanced to clinical trials that block both HSV and HIV infection by inhibiting binding and entry in vitro.

Whether blockade of entry will be sufficient to prevent sexual transmission or whether a combination strategy targeting multiple steps in the viral life cycle will be required is not yet known. Importantly, before embarking on large-scale clinical trials, more extensive evaluation of candidate microbicides, including assessment of the impact on innate defences, is warranted. Assessment of the safety and mucosal response to microbicides should be accrued from several different models including cell and organ cultures, animal models and, most importantly, pilot clinical studies.

((Excerpt of)Topical microbicides for the prevention of genital herpes infection: Marla J. Keller, Ana Tuyama, Maria Josefina Carlucci and Betsy C. Herold)

A topical microbicide that silences two genes can safely protect against genital herpes infection for as long as one week, according to a joint study by researchers at the Albert Einstein College of Medicine of Yeshiva University and Harvard Medical School.

The study, carried out in mice and published today in Cell Host & Microbe , represents a major step toward developing a vaginal microbicide that offers women convenient, long-lasting protection against herpes infection. Such a microbicide might also help in controlling the AIDS epidemic, since the blisters caused by genital herpes make people more susceptible to HIV infection. The study's principal investigators were Deborah Palliser, Ph.D., assistant professor of microbiology & immunology at Einstein and Judy Lieberman, M.D., Ph.D., professor of pediatrics, Harvard Medical School.

An estimated one in five American adults is infected with herpes simplex virus 2 (HSV-2), which causes the sexually transmitted disease known as genital herpes. Most people don't realize they're infected, since symptoms are often mild and can be mistaken for other conditions. When symptoms do occur, they usually appear as blisters on or around the genitals or rectum. When the blisters break, they leave tender sores that usually take two to four weeks to heal. HSV-2 infection is incurable and persists in the body indefinitely, although the number of outbreaks tends to decrease over time.

By combining the fast-acting-but-short-lived RNAi with the slower-acting-but-long-lived RNAi, the researchers created a vaginal microbicide offering protection that was both immediate (even warding off an HSV-2 "challenge" given shortly before the microbicide was applied) and sustained (protecting against HSV-2 challenge for a week after application).

"A good microbicide for a sexually transmitted disease must offer long-term protection-compliance will be problematic if it has to be applied immediately before sexual intercourse," says Dr. Palliser. "Our microbicide, with its two siRNAs, provided sustained and uninterrupted protection against HSV-2 infection. And equally important, we achieved these results without causing inflammation of vaginal tissue-a side effect observed with other siRNAs that also risks neutralizing a microbicide's benefits. We're hopeful that this experimental microbicide can be turned into a cost-effective therapy for use in developing countries where up to 80 percent of the population is infected with HSV-2."

(Excerpted from http://www.aecom.yu.edu/)