Sexually Transmitted Infections are on the rise. This drug could stop them.
Sexually transmitted infections (STIs) are surging across the U.S. to 2.5 million cases in 2021 according to preliminary data from the CDC. A new prevention and treatment strategy now in clinical trials may provide a way to get a handle on them.
It's easy to overlook the soaring rates of gonorrhea, chlamydia, and syphilis because most of those infections have few or no symptoms and can be identified only through testing. But left untreated, they can lead to serious damage to nerves and tissue, resulting in infertility, blindness, and dementia. Infants developing in utero are particularly vulnerable.
Covid-19 played havoc with regular medical treatment and preventive care for many health problems, including STIs. After formal lockdowns ended, many people gradually became more socially engaged, with increases in sexual activity, and may have prioritized these activities over getting back in touch with their doctors.
A second blow to controlling STIs is that family planning clinics are closing left and right because of the Dobbs decision and legislation in many states that curtailed access to an abortion. Discussion has focused on abortion, but those same clinics also play a vital role in the diagnosis and treatment of STIs.
Routine public health is the neglected stepchild of medicine. It is called upon in times of crisis but as that crisis resolves, funding dries up. Labs have atrophied and personnel have been redirected to Covid, “so access to routine screening for STIs has been decimated,” says Jennifer Mahn, director of sexual and clinical health with the National Coalition of STD Directors.
A preview of what we likely are facing comes from Iowa. In 2017, the state legislature restricted funding to family health clinics in four counties, which closed their doors. A year later the statewide rate of gonorrhea skyrocketed from 83 to 153.7 cases per 100,000 people. “Iowa counties with clinic closures had a significantly larger increase,” according to a study published in JAMA. That scenario likely is playing out in countless other regions where access to sexual health care is shrinking; it will be many months before we have the data to know for sure.
A decades-old antibiotic finds a new purpose
Using drugs to protect against HIV, either as post exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP), has proven to be quite successful. Researchers wondered if the same approach might be applied to other STIs. They focused on doxycycline, or doxy for short. One of the most commonly prescribed antibiotics in the U.S., it’s a member of the tetracycline family that has been on the market since 1967. It is so safe that it’s used to treat acne.
Two small studies using doxy suggested that it could work to prevent STIs. A handful of clinical trials by different researchers and funding sources set out to generate the additional evidence needed to prove their hypothesis and change the standard of care.
Senior researcher Victor Omollo, with the Kenya Medical Research Institute, noted, “These are prevention interventions that women can control on their own without having to seek or get consent from another person,” as is the case with condom use.
The first with results is the DoxyPEP study, conducted at two sexual health clinics in San Francisco and Seattle. It drew from a mix of transgender women and men who have sex with men, who had at least one diagnosed STI over the last year. The researchers divided the participants into two groups: one with people who were already HIV-positive and engaged in care, while the other group consisted of people who were on PrEP to prevent infection with HIV. For the active part of the study, a subset of the participants received doxy, and the rest of the participants did not.
The researchers intentionally chose to do the study in a population at the highest risk of having STIs, who were very health oriented, and “who were getting screened every three months or so as part of their PrEP program or their HIV care program,” says Connie Celum, a senior researcher at the University of Washington on the study.
Each member of the active group was given a supply of doxy and asked to take two pills within 72 hours of having sex where a condom was not used. The study was supposed to run for two years but, in May, it stopped halfway through, when a safety monitoring board looked at the data and recommended that it would be unethical to continue depriving the control group of the drug’s benefits.
Celum presented these preliminary results from the DoxyPEP study in July at the International AIDS Conference in Montreal. “We saw about a 56 percent reduction in gonorrhea, about 80 percent reduction in chlamydia and syphilis, so very significant reductions, and this is on a per quarter basis,” she told a later webinar.
In Kenya, another study is following a group of cisgender women who are taking the same two-pill regimen to prevent HIV, and the data from this research should become available in 2023. Senior researcher Victor Omollo, with the Kenya Medical Research Institute, noted that “these are prevention interventions that women can control on their own without having to seek or get consent from another person,” as is the case with condom use, another effective prevention tool.
Antibiotic resistance
Antibiotic resistance is a potentially big concern. About 25 percent of gonorrhea strains circulating in the U.S. are resistant to the tetracycline class of drugs, including doxy; rates are higher elsewhere. But resistance often is a matter of degree and can be overcome with a larger or longer dose of the drug, or perhaps with a switch to another drug or a two-drug combination.
Research has shown that an established bacterial infection is more difficult to treat because it is part of a biofilm, which can leave only a small portion or perhaps none of the cell surface exposed to a drug. But a new infection, even one where the bacteria is resistant to a drug, might still be vulnerable to that drug if it's used before the bacterial biofilm can be established. Preliminary data suggests that may be the case with doxyPEP and drug resistant gonorrhea; some but not all new drug resistant infections might be thwarted if they’re treated early enough.
“There are some tradeoffs” to these interventions, Celum says, and people may disagree on the cost of increased resistance balanced against the benefits of treating the STIs and reducing their spread within the community.
Resistance does not seem to be an issue yet for chlamydia and syphilis even though doxy has been a recommended treatment for decades, but a remaining question is whether broader use of doxy will directly worsen antibiotic resistance in gonorrhea, or promote it in other STIs. And how will it affect the gut microbiome?
In addition, Celum notes that we need to understand whether doxy will generate mutations in other bacteria that might contribute to drug resistance for gonorrhea, chlamydia or syphilis. The studies underway aim to provide data to answer these questions.
“There are some tradeoffs” to these interventions, Celum says, and people may disagree on the cost of increased resistance balanced against the benefits of treating the STIs and reducing their spread within the community. That might affect doctors' willingness to prescribe the drug.
Turning research into action
The CDC makes policy recommendations for prevention services such as taking doxy, requiring some and leaving others optional. Celum says the CDC will be reviewing information from her trial at a meeting in December, but probably will wait until that study is published before making recommendations, likely in 2023. The San Francisco Department of Public Health issued its own guidance on October 20th and anecdotally, some doctors around the country are beginning to issue prescriptions for doxy to select patients.
About half of new STIs occur in young people ages 15 to 24, a group that is least likely to regularly see a doctor. And sexual health remains a great taboo for many people who don't want such information on their health record for prying parents, employers or neighbors to find out.
“People will go out of their way and travel extensive distances just to avoid that,” says Mahn, the National Coalition director. “People identify locations where they feel safe, where they feel welcome, where they don't feel judged,” Mahn explains, such as community and family planning clinics. They understand those issues and have fees that vary depending on a person’s ability to pay.
Given that these clinics already are understaffed and underfunded, they will be hard pressed to expand services covering the labor intensive testing and monitoring of a doxyPEP regimen. Sexual health clinics don't even have a separate line item in the federal budget for health. That is something the National Association of STI Directors is pushing for in D.C.
DoxyPEP isn't a panacea, and it isn't for everyone. “We really want to try to reach that population who is most likely going to have an STI in the next year,” says Celum, “Because that's where you are going to have the biggest impact.”
Your phone could show if a bridge is about to collapse
In summer 2017, Thomas Matarazzo, then a postdoctoral researcher at the Massachusetts Institute of Technology, landed in San Francisco with a colleague. They rented two cars, drove up to the Golden Gate bridge, timing it to the city’s rush hour, and rode over to the other side in heavy traffic. Once they reached the other end, they turned around and did it again. And again. And again.
“I drove over that bridge 100 times over five days, back and forth,” says Matarazzo, now an associate director of High-Performance Computing in the Center for Innovation in Engineering at the United States Military Academy, West Point. “It was surprisingly stressful, I never anticipated that. I had to maintain the speed of about 30 miles an hour when the speed limit is 45. I felt bad for everybody behind me.”
Matarazzo had to drive slowly because the quality of data they were collecting depended on it. The pair was designing and testing a new smartphone app that could gather data about the bridge’s structural integrity—a low-cost citizen-scientist alternative to the current industrial methods, which aren’t always possible, partly because they’re expensive and complex. In the era of aging infrastructure, when some bridges in the United States and other countries are structurally unsound to the point of collapsing, such an app could inform authorities about the need for urgent repairs, or at least prompt closing the most dangerous structures.
There are 619,588 bridges in the U.S., and some of them are very old. For example, the Benjamin Franklin Bridge connecting Philadelphia to Camden, N.J., is 96-years-old while the Brooklyn Bridge is 153. So it’s hardly surprising that many could use some upgrades. “In the U.S., a lot of them were built in the post-World War II period to accommodate the surge of motorization,” says Carlo Ratti, architect and engineer who directs the Senseable City Lab at Massachusetts Institute of Technology. “They are beginning to reach the end of their life.”
According to the 2022 American Road & Transportation Builders Association’s report, one in three U.S. bridges needs repair or replacement. The Department of Transportation (DOT) National Bridge Inventory (NBI) database reveals concerning numbers. Thirty-six percent of U.S. bridges need repair work and over 78,000 bridges should be replaced. More than 43,500 bridges are rated in poor condition and classified as “structurally deficient” – an alarming description. Yet, people drive over them 167.5 million times a day. The Pittsburgh bridge which collapsed in January this year—only hours before President Biden arrived to discuss the new infrastructure law—was on the “poor” rating list.
Assessing the structural integrity of a bridge is not an easy endeavor. Most of the time, these are visual inspections, Matarazzo explains. Engineers check cracks, rust and other signs of wear and tear. They also check for wildlife—birds which may build nests or even small animals that make homes inside the bridge structures, which can slowly chip at the structure. However, visual inspections may not tell the whole story. A more sophisticated and significantly more expensive inspection requires placing special sensors on the bridge that essentially listen to how the bridge vibrates.
“Some bridges can afford expensive sensors to do the job, but that comes at a very high cost—hundreds of thousands of dollars per bridge per year,” Ratti says.
We may think of bridges as immovable steel and concrete monoliths, but they naturally vibrate, oscillating slightly. That movement can be influenced by the traffic that passes over them, and even by wind. Bridges of different types vibrate differently—some have longer vibrational frequencies and others shorter ones. A good way to visualize this phenomenon is to place a ruler over the edge of a desk and flick it slightly. If the ruler protrudes far off the desk, it will vibrate slowly. But if you shorten the end that hangs off, it will vibrate much faster. It works similarly with bridges, except there are more factors at play, including not only the length, but also the design and the materials used.
The long suspension bridges such as the Golden Gate or Verrazano Narrows, which hang on a series of cables, are more flexible, and their vibration amplitudes are longer. The Golden Gate Bridge can vibrate at 0.106 Hertz, where one Hertz is one oscillation per second. “Think about standing on the bridge for about 10 seconds—that's how long it takes for it to move all the way up and all the way down in one oscillation,” Matarazzo says.
On the contrary, the concrete span bridges that rest on multiple columns like Brooklyn Bridge or Manhattan Bridge, are “stiffer” and have greater vibrational frequencies. A concrete bridge can have a frequency of 10 Hertz, moving 10 times in one second—like that shorter stretch of a ruler.
The special devices that can pick up and record these vibrations over time are called accelerometers. A network of these devices for each bridge can cost $20,000 to $50,000, and more—and require trained personnel to place them. The sensors also must stay on the bridge for some time to establish what’s a healthy vibrational baseline for a given bridge. Maintaining them adds to the cost. “Some bridges can afford expensive sensors to do the job, but that comes at a very high cost—hundreds of thousands of dollars per bridge per year,” Ratti says.
Making sense of the readouts they gather is another challenge, which requires a high level of technical expertise. “You generally need somebody, some type of expert capable of doing the analysis to translate that data into information,” says Matarazzo, which ticks up the price, so doing visual inspections often proves to be a more economical choice for state-level DOTs with tight budgets. “The existing systems work well, but have downsides,” Ratti says. The team thought the old method could use some modernizing.
Smartphones, which are carried by millions of people, contain dozens of sensors, including the accelerometers capable of picking up the bridges’ vibrations. That’s why Matarazzo and his colleague drove over the bridge 100 times—they were trying to pick up enough data. Timing it to rush hour supported that goal because traffic caused more “excitation,” Matarazzo explains. “Excitation is a big word we use when we talk about what drives the vibration,” he says. “When there's a lot of traffic, there's more excitation and more vibration.” They also collaborated with Uber, whose drivers made 72 trips across the bridge to gather data in different cars.
The next step was to clean the data from “noise”—various vibrations that weren’t relevant to the bridge but came from the cars themselves. “It could be jumps in speed, it could be potholes, it could be a bunch of other things," Matarazzo says. But as the team gathered more data, it became easier to tell the bridge vibrational frequencies from all others because the noises generated by cars, traffic and other things tend to “cancel out.”
The team specifically picked the Golden Gate bridge because the civil structural engineering community had studied it extensively over the years and collected a host of vibrational data, using traditional sensors. When the researchers compared their app-collected frequencies with those gathered by 240 accelerometers formerly placed on the Golden Gate, the results were the same—the data from the phones converged with that from the bridge’s sensors. The smartphone-collected data were just as good as those from industry devices.
The study authors estimate that officials could use crowdsourced data to make key improvements that would help new bridges to last about 14 years longer.
The team also tested their method on a different type of bridge—not a suspension one like the Golden Gate, but a concrete span bridge in Ciampino, Italy. There they compared 280 car trips over the bridge to the six sensors that had been placed on the bridge for seven months. The results were slightly less matching, but a larger volume of trips would fix the divergence, the researchers wrote in their study, titled Crowdsourcing bridge dynamic monitoring with smartphone vehicle trips, published last month in Nature Communications Engineering.
Although the smartphones proved effective, the app is not quite ready to be rolled out commercially for people to start using. “It is still a pilot version,” so there’s room for improvement, says Ratti, who co-authored the study. “But on a more optimistic note, it has really low barriers to entry—all you need is smartphones on cars—so that makes the system easy to reach a global audience.” And the study authors estimate that the use of crowdsourced data would result in a new bridge lasting about 14 years longer.
Matarazzo hopes that the app could be eventually accessible for your average citizen scientist to collect the data and supply it to their local transportation authorities. “I hope that this idea can spark a different type of relationship with infrastructure where people think about the data they're collecting as some type of contribution or investment into their communities,” he says. “So that they can help their own department of transportation, their own municipality to support that bridge and keep it maintained better, longer and safer.”
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
The Friday Five: Sugar could help catch cancer early
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the promising studies covered in this week's Friday Five:
- Catching cancer early could depend on sugar
- How to boost memory in a flash
- This is your brain on books
- A tiny sandwich cake could help the heart
- Meet the top banana for fighting Covid variants