New Treatment for Gonorrhea Prevents Reinfection

A nanoparticle-based cancer therapy has been found to thwart an antibiotic-resistant, sexually transmitted infection in mice

A first step has been taken toward a treatment for gonorrhea, a sexually transmitted disease (STD) notorious for its high reinfection rates. This news comes within days of a troubling update from the U.S. Centers for Disease Control that placed the STD on a list of “urgent threats”(PDF) in the fight against drug-resistant bacteria. According to the CDC, Neisseria gonorrhoeae, the bacteria that causes the malady in humans—which can initially result in painful inflammation and discharge, and can cause infertility and even death if not treated—requires urgent and aggressive action from the medical research community. Researchers from the University at Buffalo, S.U.N.Y., think the answer may lie in marshaling the immune system against gonorrhea.

The study, published in The Journal of Infections Diseases, found gonococcal infections in mice could be cured by introducing into the genital tract a cytokine, or immunoregulatory protein, known as interleukin-12 (IL-12), which is also being investigated as a cancer-fighting agent. Michael Russell, a microbiologist and immunologist at S.U.N.Y. Buffalo and one of the study’s authors, says that his 20-year investigation into gonorrhea and its resilience led him to suspect that it was actively altering immune systems, preventing human hosts from developing long-term resistance to it.

The exact mechanism of the alteration remains unclear, but Russell thinks it has to do with the two distinct “arms” of vertebrate immune systems: innate and adaptive. Russell observed high levels of a cytokine called interleukin-10 (IL-10) in gonococcal infections, and observed that it induces an innate immune response. IL-10 seems to suppress adaptive responses—like the formation of antibodies that can be used again to fight later infections—in favor of more general, short-term innate responses. Meanwhile, the innate responses, such as inflammation, are easy for N. gonorrhoeae to beat. If IL-12 could counteract the effects of IL-10, Russell hypothesized, it could help the body fight gonorrhea more effectively, and could be used in a treatment for the STD. When his colleague Nejat Egilmez developed a new delivery mechanism for the otherwise toxic IL-12, in which microspheres of slow-releasing nanoparticles of the cytokine could be targeted directly onto immunosuppressant tumors, Russell’s team decided to try injecting them into the vaginal tracts of infected mice.

Not only did mice treated with IL-12 respond more quickly to antibiotics, they were also significantly less likely to be reinfected than controls when exposed to the same strain a month later. “We found that the IL-12 treatment allows the development of an adaptive immune response not usually seen,” Russell says. It seems that by counteracting the IL-10 present at gonococcal infections, the treatment prevents immune systems from being tricked out of developing adaptive responses to the disease. The effect, he says, lasts for several months.

The results come just in time, as the CDC now reports(PDF) that of the 800,000 estimated cases of gonorrhea that occur each year in the U.S., at least 30 percent are resistant to current antibiotic treatments. With 23 percent of cases now resistant to tetracycline, the CDC recommends that gonococcal infections be treated with a combination of two antibiotics—ceftriaxone in combination with either azithromycin or doxycycline—although a slow but steady increase in strains resistant to ceftriaxone indicate this combination may soon be useless as well.

The new treatment would increase the antibiotics’ effectiveness, but researchers hope that one day it might wean us off the drugs for good. “Since the second world war,” Russell says, “we’ve been treating infections by throwing antibiotics at them. Now that bacteria are emerging with antibiotic resistance, we have nothing else in the pipeline to deal with gonorrhea.” But the IL-12 treatment, he says, can turn the infection into a “live vaccine,” allowing the body to develop immunity. He hopes that further research will show a resistance that carries over from strain to strain, indicating his team has paved the way for a gonorrhea vaccine.

Sanjay Ram, an infectious disease specialist at the University of Massachusetts Memorial Medical Center who was not affiliated with the study, called the work “extremely important,” adding that it “provides nice clues for vaccine development. It would be useful in high-risk women who get repeat infections, with the first occurrence acting as a vaccine for subsequent infections.” Caution is necessary, however, he notes—there are differences between the immune systems of mice and humans, and we’re not sure what high levels of IL-12 might do to a human genital tract. One worry in particular is that higher levels of T cells, which IL-12 stimulate, would mean higher levels of so-called T helper, or CD4, cells. Although vital to the immune system, these cells are also a vulnerable point at which HIV can enter the body. Having high levels of them in the genital tracts of at-risk women would be troubling. But, Ram says, with the state of crisis created by the disease’s advance, any lead is a promising one. "One could go on and on about possible downsides,” he says, “but the fact is that we have a multidrug-resistant disease on our hands.”

The STD crisis notwithstanding, Russell says that human application is a long way off. First, he will see just how long and how effectively IL-12 therapy can protect mice from the rapidly mutating bacteria. He also hopes to learn more about the exact mechanism by which the IL-12 cytokines stimulate the immune responses seen in the study. The answer remains largely a mystery and would have to be documented before human trials could commence. But eventually he hopes to see this novel approach to the treatment of infectious diseases—the stimulation of an immune response at the site of infection—deployed to fight gonorrhea, along with other diseases.

I knew a few guys who would go to a local doc and pay cash to keep it out of their medical records. There was a certain group who went to the local doc BEFORE going out.

“Hey, you boys got burn?”

“No Doc, but we know we gonna catch it!”

well, I can’t help it

In ‘11 we visited the Museum of Naval Aviation in Pennsecola. I was anxious to visit the restaurant because it is the reconstructed Cubi Point officer’s club. It was our favorite and better than the Subic Club.

I was very surprised. It was not as I remembered at all. Nothing was familiar. I finally found our OICC plaque....... we built it, among all the hundreds of squadron plaques.

It dawned on me that I was old as hell. What they had reconstructed was the New O club. It was almost finished when we left in July ‘67. I was forgetting there had been 40 years in the meantime

On the night my son was born I spent several hours in the Cubi BOQ bar. It was closer to the hospital and the only thing open in the middle of the night

Prior to living on base at Subic, We lived in Manila. While waiting for housing, I flew back and forth every day.

It was great. We built all sorts of stuff and worked our butts off to get it done ASAP.

True story.. Viet Nam 1971 Flight platoon Chinook helicopter company. A fair haired child name of Stan admitted that he was a virgin. The wild hooligans of the flight platoon decided that this injustice needed immediate remedy ! A nice young sweet thang that was of the proper temperament was hired to do the job. Both virgin and devirginee were appropriately lubricated with alcohol and placed in the only room in flight platoon barracks that had a door. Wild rock and roll music and much ribald encouragement was offered while the maneuver was accomplished. After an appropriate length of time Stan came out clothed in a towel and proceeded to go to the shower room for a postcoital bath. All was well until 4 days later when a horrible sound was heard to roll through the flight platoon.An emergency search was instituted to put the poor animal out of its misery. Turned out it was Stan who was standing at the latrine holding a body part and moaning and groaning. HE was dispatched to the sick call where he was innoculated with 4.8 million units of penicillin with a needle that resembled the harpoon used on moby dick (Thank you Mr. Melville) WE felt really bad that we had contributed to the nefarious deed, but it seems that all came out in the end to the satisfaction of all. Stan, where ever you are, I hope you forgave us.....

Actually, from the 1920s to the 1940s, many blacks were deathly afraid of hospitals because of rampant rumors that medical students would experiment on them. The one exception was when women gave birth.

Often the parents either had no idea of what to name their children, or wanted a better name, an uncommon name. So they would ask doctors and even interns to name their baby.

Often they would give them the names of great Roman and Greek leaders, like Scipio Africanus, or Hannibal, the enemy he defeated. But sometimes they would give them names from medical words, like “Spirochete Jones”, and “Priapism Smith”.

Perhaps the most insulting was “Oligoneuronic” last name unknown. That is a Latin term meaning “few brain cells”.

One of the most appropriate names for a girl was pronounced “Femalee”, a typographic error on the birth certificate which put the gender “Female” under “name”. But you have to admit, it is a very appropriate name for a girl.

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