Standard treatment for common STD doesn't eliminate parasite in some women

A new study led by an infectious disease epidemiologist at Tulane University School of Public Health and Tropical Medicine could change the way doctors treat a common sexually transmitted disease.

Professor Patricia Kissinger and a team of researchers found the recommended single dose of medication isn't enough to eliminate trichomoniasis, the most common curable STD, which can cause serious birth complications and make people more susceptible to HIV. Results of the research are published in Lancet Infectious Diseases.

Globally, an estimated 143 million new cases of trichomoniasis among women occur each year and most do not have symptoms, yet the infection is causing unseen problems. The recommended treatment for more than three decades has been a single dose of the antibiotics metronidazole or tinidazole.

The researchers recruited more than 600 women for the randomized trial in New Orleans; Jackson, Mississippi; and Birmingham, Alabama. Half the women took a single dose of metronidazole and the other half received treatment over seven days.

Kissinger and her team found the women who received multiple doses of the treatment were half as likely to still have the infection after taking all the medication compared to women who only took a single dose.

"There about 3.7 million new cases of trichomoniasis each year in the United States," Kissinger said. "That means a lot of women have not been getting inadequate treatment for many decades."

Trichomoniasis can cause preterm delivery in pregnant women and babies born to infected mothers are more likely to have low birth weight. The parasite can also increase the risk of getting or spreading HIV.

Kissinger believes the CDC will change its treatment recommendations because of the results of this study.

"We need evidence-based interventions to improve health," Kissinger says. "We can no longer do something because it's what we've always done. I hope that this study will help to change the recommendations so that women can get the proper treatment for this common curable STD."

Source: https://www.sciencedaily.com/releases/2018/10/181007084044.htm

No more ‘sledgehammer’: As gonorrhea grows resistant to antibiotics, researchers look to bespoke treatments

With antibiotic resistance on the rise, the days when doctors and clinics could rely on one treatment to cure all gonorrhea cases may be waning.

In fact, clinicians may find that some of their patients respond best to drugs of the past. But how will they know which patients?

To answer that question, a handful of researchers and companies are trying to develop rapid, point-of-care diagnostics that would signal which drugs work for a given patient and permit clinicians to tailor treatment to the bacterial strain. A future, in other words, of bespoke treatment, in which a greater variety of drugs are used to treat a very common sexually transmitted disease — potentially prolonging the utility of several antibiotics.

“It would allow for smarter medicine,” Dr. Jeffrey D. Klausner, a professor of infectious diseases medicine at the University of California, Los Angeles, told STAT. “Right now, we’re treating gonorrhea with a sledgehammer, we’re treating everything with the same exact regime. And it’s not a surprise that the organism will become resistant to what we’re currently using.”

Klausner has collaborated with several companies working in this area but has not received payment from the companies. The companies have made contributions to UCLA, he said.

Gonorrhea is spread by sexual contact, and infection can occur in the genitals, the rectum, and the throat. The World Health Organization estimates that about 78 million people a year are infected with gonorrhea; roughly 820,000 of those infections occur in the United States.

Left untreated, gonorrhea can cause pelvic inflammatory disease and infertility in women and sterility in men. Infection increases a person’s risk of contracting HIV. Babies born to an infected woman can develop blindness.

From a treatment point of view, the ideal regimen for curing gonorrhea is an oral antibiotic — and was long the standard of care. But gonorrhea is a wily bacterium, adept at learning tricks that allow it to evade the power of antibiotics. One after another, the available drugs have started to fail.

For several years, the recommended regimen for gonorrhea has been a dual-therapy approach, the thinking being that it is harder for resistance to develop to a drug combination than to a single drug. The current recommended therapy is one injection of the antibiotic ceftriaxone followed by a multiday course of azithromycin. But even that approach is starting to show signs of weakness.

At the same time, there has been a belief that, even as medicine has moved on, there is life left in the drugs that have been abandoned — if you could figure out in whom they would work.

“We’ve been treating empirically and a lot of times ignoring the fact that the majority of organisms, the majority of infections we’re seeing, are actually fully susceptible to the old drugs,” said Fred Tenover, vice president for scientific affairs at Cepheid Inc., a California-based maker of molecular diagnostics.

“So now we have to have a change in philosophy and say: You know what? Now it’s time to go and do what we do for every other infection, which is actually define what the best therapeutic is up front.”

Cepheid is exploring the idea of developing such a test, Tenover said. “We’re trying to figure out what it would look like and what it would cost,” he said. “This is not in our pipeline officially. It’s something we’re looking at, something we haven’t committed to, but we have figured out how to make the assay.”

Other smaller companies are in the hunt. SpeeDx, an Australian-American firm, has a test in development that it hopes will receive licensing approval in Europe this autumn. The company is currently conducting a clinical trial in the United States in hopes of with the goal of filing for approval with the Food and Drug Administration.

The test both diagnoses gonorrhea and indicates whether the infecting strain can be treated with Cipro, said CEO Colin Denver. It currently would need to be processed by a central lab, but the plan is to develop the assay as a point-of-care test that could be used in a clinic or doctor’s office.

Shield Diagnostics, of Santa Clara, Calif., has a similar idea in mind. The company has a proprietary testing platform; CEO Fred Turner said it will roll out its first test this fall. The test can diagnose gonorrhea and ascertain if the strain is susceptible to Cipro.

For now, it is not a point-of-care test; that may be three or four years down the road, Turner said. In the meantime, Shield will process the tests in its own laboratories. Turner said the testing will likely take two to three days. Ideally, over time, both companies hope their assays will be expanded to give a broader resistance profile, one that indicates whether other drugs would be effective.

“Our ultimate goal is to have clinicians utilize a test-and-treat algorithm so that you don’t have to use these empiric therapies,” Denver said.

A patient would come into a clinic and specimens to test would be taken. While he or she is seeing the doctor, the test would be run. Within an hour or so, the doctor would know whether a single dose of Cipro or cefixime (also an oral drug) would do, or whether the ceftriaxone-azithromycin combination would be the better option.

“It’s like personalized medicine — your individual infection treated with the antibiotic you know is going to work,” Denver said.

But in order for these types of tests to be truly useful, they’ll need to be affordable and produce a rapid answer, said Dr. Lindley Barbee, an assistant professor of infectious diseases at the University of Washington and medical director of the Public Health – Seattle & King County STD Clinic. Not a day or two later, but while the person was in the clinic.

Many clinics that treat sexually transmitted infections are government funded, Barbee noted: “You have to get the cost low enough to make it worthwhile.”

That’s clearly a factor that has slowed development of these tests. “If you say to somebody who’s paying $10 for this test now, ‘Well, I can better define your therapy but it’s going to cost $17 a test, not $10 a test,’ that may be beyond the reach of a lot of public health clinics or STI clinics. And that’s probably what it would take,” said Cepheid’s Tenover.

“To date the return on investment has not been positive enough to make these commercially available,” he said. “That may be changing. And I think as we talk more and more about the spread of superbug gonorrhea, people may be more and more interested in doing this. But in the past there hasn’t been a market for these types of tests.”

Source: https://www.statnews.com/2018/07/17/gonorrhea-grows-resistant-to-antibiotics-researchers-look-to-bespoke-treatments/

Gonorrhea researchers identify novel route to vaccine, new antibiotic

Researchers have identified a protein that powers the virulence of the bacteria that causes gonorrhea, opening the possibility of a new target for antibiotics and, even better, a vaccine.

The findings, published today in PLOS Pathogens, are especially important since the microbe, Neisseria gonorrhoeae, is considered a "superbug" because of its resistance to all classes of antibiotics available for treating infections.

Gonorrhea, a sexually transmitted disease that results in 78 million new cases worldwide each year, is highly damaging if untreated or improperly treated.

It can lead to endometritis, pelvic inflammatory disease, ectopic pregnancy, epididymitis and infertility. Babies born to infected mothers are at increased risk of blindness.

"The infections very often are silent," said Oregon State University researcher Aleksandra Sikora. "Up to 50 percent of infected women don't have symptoms, but those asymptomatic cases can still lead to some very severe consequences for the patient's reproductive health, miscarriage or premature delivery."

The need for better antibiotic therapy, and a vaccine, is pressing. N. gonorrhoeae strains resistant to the last effective treatment options have emerged, and failures in treatment are occurring.

Sikora and her research team at the OSU/OHSU College of Pharmacy and Ann Jerse's lab at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, collaborated to discover a novel lipoprotein that N. gonorrhoeae uses to defeat the body's first line of innate immune defense.

The body relies on enzymes known as lysozymes that, as their name suggests, thwart bacteria by causing their cell wall to lyse, or break apart. Lysozymes are abundant both in epithelial cells, which make up the tissue on the outside of organs and the inside of body cavities, and in the phagocytic cells that protect the body by ingesting foreign particles and bacteria.

In turn, many gram-negative bacteria -- characterized by their cell envelope that includes a protective outer membrane -- have developed ways of defeating lysozymes. Prior to the work by Sikora's team, however, only one lysozyme-fighting protein had been discovered in the Neisseria genus.

Now that new targets have been identified, they can be explored as bullseye candidates for new antibiotics or a vaccine -- if the lysozyme inhibitor can itself be inhibited, then the bacteria's infection-causing ability is greatly reduced.

Sikora and her collaborators named the new protein SliC, short for surface-exposed lysozyme inhibitor of c-type lysozyme.

Studying SliC's function in culture as well as in a gonorrhea mouse model -- mice were infected with N. gonorrhoeae, then checked for SliC expression at one, three and five days -- researchers determined the protein was essential to bacterial colonization because of its anti-lysozyme role.

"This is the first time an animal model has been used to demonstrate a lysozyme inhibitor's role in gonorrhea infection," Sikora said. "Together, all of our experiments show how important the lysozyme inhibitor is. This is very exciting."

Source: https://www.sciencedaily.com/releases/2018/07/180705143834.htm

Abstract submission for the conference STD 2018 held at Toronto, Canada on August 20-21, 2018 is welcome!! Submit your abstract here: https:/std-hiv-aids.cmesociety.com/abstract-submission

History of Gonorrhea

Gonorrhoea is a sexually transmitted infection that has been known to mankind since medieval times. It was referred to as the “clap” before the actual cause was discovered.

Discovery of the infection and its cause

The exact time when gonorrhoea started cannot be ascertained. Earliest records of the disease are found from 1611 when the English parliament enacted a law to ensure that the spread of the infection is decreased and curbed. This shows the magnitude of the public health problem this infection had posed then. However, even then the cause of the infection was unknown.

This was followed by a similar law in 1256 in France during the reign of Louis IX. The symptoms of the infection were observed when the crusaders lay siege of Acre. After the Pope Boniface secularized the practice of medicine, the doctors began to treat common men as well as prostitutes for this infection.

In 1879 Neisser discovered the gonococcus or Neisseria gonorrhoeae and it was soon proven to be the causative agent of gonorrhoea. He demonstrated its presence consistently in patients with symptoms. In addition, when discharge and cultures of gonococci was introduced into the urethra of healthy men, it caused the disease

History of gonorrhea treatments

The earliest treatment of gonorrhea was with the use of mercury. Earliest findings from an English warship “Mary Rose” show that several special surgical tools were used to inject mercury via the urinary opening.

In the 19th century gonorrhea was treated with the help of silver nitrate. Silver nitrate was soon discontinued and instead protargol was used which was a type of colloidal silver sold by Bayer from the year 1887.

Around 1859 another treatment was popular. These were cubebs, an Indonesian variety of pepper of which the dried powdered unripe fruit was used, and balsam of copaiba (or copaiva), which was extracted from a South American tree. The indication of their effectiveness was cessation of the discharge.

In the 1890s the first vaccine prepared from killed gonococci taken from Neisser’s laboratory. This vaccine was introduced in 1909.

Before antibiotics came into being metals were tried against the infection this included arsenic, antimony, bismuth, gold etc.

The use of other drugs for treatment continued right until the 1940s till antibiotics – notably Penicillin - came into use. Other antibiotics that arose during this time were the sulphur compounds or Sulphanilamide, Sulfapyridine and sulfathiazol.

Penicillins continued to be mainstay of therapy until 1970’s. In 1980 the first gonococcus isolates were identified that were resistant to penicillin. In 1983 a local epidemic caused by a penicillin resistant strain occurred in North Carolina. Patients were successfully treated with spectinomycin.

Share your ideas and gain more knowledge on advancements in clinical therapies of STD from experts around the world, to know more about the scientific sessions of the conference STD 2018, please visit: https://std-hiv-aids.cmesociety.com/call-for-abstracts/

Source: https://www.news-medical.net/health/Gonorrhea-History.aspx