UPMC to boost sexually transmitted infections research

By Julie Percha

When Arkansas native Toni Darville moved to Pittsburgh two years ago, she was looking for… When Arkansas native Toni Darville moved to Pittsburgh two years ago, she was looking for chlamydia.

She had studied the sexually transmitted disease for more than 12 years, most recently on mice models at the University of Arkansas, and was ready to move on to clinical trials.

Now Darville, the current chief of pediatric infectious diseases at Children’s Hospital of Pittsburgh of UPMC, has her opportunity, thanks to a $12.5 million grant from the National Institutes of Health.

“There were already some great people here doing research on women’s health, so it was really attractive for me to come here and develop collaboration,” Darville, the principal investigator, said. “The collaborative atmosphere at the University of Pittsburgh is really what enabled us to get this grant.”

The five-year grant will help Darville and three colleagues establish the UPMC Sexually Transmitted Infections (STI) Cooperative Research Center, a collaborative effort between UPMC and Magee-Womens Hospital to research female reproductive complications caused by sexually transmitted infections.

The NIH’s National Institute of Allergy and Infectious Diseases issued grants to fund four to six similar STI research centers nationwide, totaling $10.2 million in awards.

The grant that UPMC’s center received will fund four separate research initiatives, including projects headed by Darville; Harold Wiesenfeld, associate investigator at Magee-Womens Research Institute; Sharon Hillier, director of reproductive infectious disease research at Magee; and Thomas Cherpes, researcher at Magee.

One of the projects focuses on the treatment of pelvic inflammatory disease, or PID, a bacterial infection in the upper female genital tract. According to the Centers for Disease Control and Prevention, more than 1 million U.S. women experience PID annually, causing damage to their fallopian tubes and ovarian tissue. The disease, which is commonly caused by STIs such as chlamydia and gonorrhea, is serious and can cause chronic pelvic pain, ectopic pregnancies or infertility.

Another project aims to identify the types of bacteria that cause bacterial vaginosis, a condition that disrupts the normal balance of bacteria in the vagina. The complication causes burning, cervical discharge and contractions, which can lead to premature births in pregnant women, according to the CDC.

“It’s very common ¬— a lot more common than you’d think,” Darville said.

The third research endeavor will identify the immune response that is most associated with protection against chlamydia. This project will additionally collaborate with Genocea Biosciences, a vaccine development company, to help create a vaccine for the STI.

In addition to leading the STI research center, Darville also heads the fourth research project to be funded through the NIH grant. Her research focuses on the role of receptor signaling with chlamydia, using a mouth model to simulate pathogenesis.

The CDC estimates that chlamydia is the most common bacterial STI, with more than 1.03 million cases reported in the United States in 2006. The disease is often “silent,” with mild or absent symptoms — including discharge, abdominal pain or a burning sensation — that can surface up to three weeks after exposure.

Both men and women can contract chlamydia, but its effects are not equal between genders.

“Men basically spread the disease. Women bear the brunt of it,” Darville said. She said that men experience few longterm complications, whereas women commonly have scarring on their fallopian tubes, which leads to infertility.

The disease is easily treatable with antibiotics, but for women who don’t know they’re infected, the effects can be long-lasting.

“Chlamydia is the leading cause of involuntary infertility in the world,” she said. “If your fallopian tubes are scarred, then there’s nothing you can do.”

An estimated 10 percent of teenage girls, ages 15-19, are infected with the disease, with the most incidences of the disease occurring in adolescence.

Research with the grant money is already underway, and Darville hopes to move into clinical trials shortly.

With the NIH grant money, researchers hope to better diagnose and treat the infection, as well as determine the best therapy for women who have STIs.

“We [aim to] improve women’s health care — hopefully discover novel antigens that may accelerate or push forward our ability to develop a chlamydia vaccine,” she said.

In addition to supporting research endeavors, the grant money will also be used for an administrative core to staff the research center.

The grant will allow the center to hire a secretarial staff to organize meetings and collaboration sessions, as well as a clinical core of nurses and staff members to recruit patients to the study.

Because the research center is focused on collaboration between UPMC and Magee researchers, the investigators are also able to share clinical samples from their trials.

Patients who participate in the studies might supply multiple samples, which will be used among the four projects.