THE BATTLE AGAINST THE “enemy in your pants”—as cheeky World War II-era posters referred to syphilis and gonorrhea—is as old as medicine itself and has a long history of mixing moral judgment with medical solutions. Beginning in 1917, social hygiene crusaders in the United States would identify and forcibly examine prostitutes and other women thought to be spreading “venereal diseases,” sometimes even throwing them in jail. During the Depression, a positive syphilis test could disqualify a job applicant, and until the 1980s, negative syphilis tests for a prospective bride and groom were required before a marriage license could be issued.

The sexual revolution may have changed how public health leaders think of sexually transmitted diseases (STDs), yet the problem of how to curb their spread hasn’t gone away—and may, in fact, have gotten worse. With the incidence of STDs surging to nearly 2.3 million reported cases in 2017, according to the Centers for Disease Control and Prevention, the United States has the highest rate of infection among industrialized countries. Over the past four years, reported cases of syphilis have increased by 76%, gonorrhea by 67% and chlamydia, the most prevalent STD, by 22%. And those figures don’t count those who haven’t sought treatment or don’t know they’re infected.

There has also been a 153% rise since 2013 in congenital syphilis in babies born to infected mothers, with 918 cases reported in 2017. This form of the disease is devastating, killing four of 10 infected offspring in the womb or shortly after birth, and those who survive often have deformed bones, are blind or deaf and may have other long-term problems. “In the past, a positive syphilis test in a pregnant woman was considered an emergency and everything was done to make sure she got treatment,” says Jeffrey Klausner, professor of medicine and global health at UCLA Fielding School of Public Health and former director of STD Prevention and Control Services at the San Francisco Department of Public Health. But over the past 15 years, state and local STD programs have had to contend with a 40% cut in federal funding. “Today, public health departments are so short-staffed and underfunded that there may be no follow-up at all for that woman,” Klausner says.

With the rise in the number of STDs comes other problems. “Because there is more syphilis around, we’re seeing rare complications more frequently,” says Kevin Ard, an infectious diseases specialist at Massachusetts General Hospital and medical director of the National LGBT Health Education Center at the Fenway Institute in Boston. “I’ve seen patients with hepatitis caused by syphilis; ocular syphilis, which can cause blindness; and syphilis in the brain.”

With gonorrhea, the challenge is to outwit a wily organism that has become resistant to each of the seven classes of antibiotics used to treat it since 1938. It may be gaining resistance to the current drug regimen, and a handful of recent cases have resisted all antibiotics that are normally effective against the organism, responding only to antibiotics of last resort. “If drug-resistant gonorrhea spread in this country, it would be a catastrophe,” says Ard, who notes that MGH has been part of a national surveillance project that monitors gonorrhea strains for microbial resistance.

Yet while treating some cases of gonorrhea may be complex, most STDs respond to uncomplicated and effective therapies. In other words, curing these diseases isn’t the most vexing problem. The challenge is locating an ever-shifting population of infected people and providing treatment quickly enough to slow the spread of disease in an expanding network of partners who are also infected. Curbing the boom in the big three STDs will take ingenuity, clever epidemiology and, perhaps, innovations in diagnosis and treatment.

THE PICTURE WAS NOT always so grim. In 1999 the CDC predicted that syphilis could soon be eliminated in the United States—that is, there would be fewer than 1,000 new cases reported nationally each year. There were just 5,979 reported cases of primary and secondary syphilis (the infectious stages) in 2000, an all-time low. But syphilis began to rise again, mostly in men who sleep with men, or MSM, who in 2017 accounted for about 68% of syphilis cases.

Men have experienced the sharpest rise in gonorrhea, with the number of reported cases up 86.3% from 2013 to 2017, another sign that infections are on the rise in the gay, bisexual and MSM communities. Two-thirds of chlamydia cases are in people 15 to 24 years old, and that infection is found more often in women than in men, largely because clinical guidelines call for women under the age of 26 to be screened for chlamydia during annual gynecological checkups. But the overall number of cases of chlamydia is thought to be vastly underreported. “Only 40% of young women are being screened,” says Edward W. Hook III, an infectious disease specialist at the University of Alabama at Birmingham. Adds Klausner, “The CDC estimates that there are almost three million cases of chlamydia annually, which means we’re finding fewer than half of them.”

The advent of hookup apps—social net-working sites that connect adults with willing sexual partners in their area, often with a degree of anonymity—is one part of the changing landscape. “Syphilis has really found a home in people who use phone apps to find nearby sexual partners,” says Bradley Stoner, associate professor of medicine at the Washington University School of Medicine in St. Louis and former chief of STD Services for the St. Louis County Department of Public Health. Most health departments have active partner notification programs for those infected by syphilis or human immunodeficiency virus (HIV), which can cause the most serious and lasting effects. “But syphilis has gotten a boost with these apps, because people don’t know their partners and can’t get in touch with them when an infection is diagnosed,” he says.

A rise in all of these diseases at once can have a compounding effect, as co-infections often make STDs harder to treat. “Gonorrhea inhibits the immune system, so people who are also infected with chlamydia have a harder time clearing the infection and tend to get reinfected repeatedly,” says Toni Darville, division chief of pediatric infectious disease and vice chair of pediatric research at the University of North Carolina School of Medicine in Chapel Hill.

A particular problem for MSM is the added risk that they’ll acquire HIV, the virus that causes AIDS. “Half of MSM who are diagnosed with syphilis are found to have HIV as well,” says Kyle Bernstein, chief of the epidemiology and statistics branch in the Division of STD Prevention at the CDC. “An MSM with syphilis is probably involved in a high-risk sexual network in which there is a lot of HIV,” he says. But there may be biological as well as behavioral reasons for co-infection. Inflammation from an STD recruits the immune system’s CD4 cells to the site of the infection. “These are the very cells that HIV uses to gain entry into the body,” says Stoner.

MSM who are HIV-positive also tend to acquire more STDs than those who don’t have the virus. Compromised immunity from HIV may be to blame, but one group of researchers believes antiretroviral therapy for HIV could reduce immune responses so that people become more susceptible to syphilis.


Poster art by Oliver Munday

CONDOMS EFFECTIVELY PREVENT STDS—witness Nevada brothels, which have cut HIV infection rates to zero by requiring all men to use them. And during the 1980s, when fear of HIV scared many people into scrupulously using condoms, that helped control other STDs as well. But the advent of effective antiretroviral therapy in the mid-1990s made HIV a manageable chronic disease, reducing anxiety about getting the virus and increasing the prevalence of condomless sex.

And just as the numbers of STD infections have risen, funding cutbacks have shortchanged efforts to control the epidemic. With budgets squeezed, health departments have had to get creative. “They’ve become savvy about using the hook-up apps to do public health work, including contact tracing and STD messaging, which might include information about outbreaks or a link to get a confidential home-testing kit for free,” says Amanda Dennison, director of programs and partnerships at the National Coalition of STD Directors. Some health departments send vans to nightclubs and bars, offering free STD screening, while other states offer recurring shipments of free mail-order condoms to at-risk people who request them. In some states, clinicians can practice expedited partner therapy, providing patients diagnosed with chlamydia or gonorrhea prescriptions or medications to give to their partners.

“The hottest innovation today is sexual network analysis,” says Kari Haecker, program manager for HIV/STD Prevention and Control Services in Clark County, Wash. In Haecker’s previous job as field operations supervisor for the STD control program in Indianapolis, she faced the challenge of controlling STDs in a city that had the highest rate of syphilis per capita in the world in 1999 to 2000. “We had 407 cases of primary and secondary syphilis that year, which was related to an epidemic of crack cocaine,” Haecker says.

Using the information they had on file about the sexual practices and partners of those treated for syphilis, Haecker created a map of about 200 gay men connected in a high-risk sexual “network” of those likely to have sex with each other. When one person in that group tested positive for syphilis, public health workers immediately began knocking on the doors of those in the network who hadn’t recently been screened for STDs and offered them a syphilis blood test on the spot. “You’re not making enough of an effort unless you’re drawing blood on someone’s porch or in their kitchen,” says Haecker. One meth user in the network even offered his home as a screening venue.

The network map helped the health department predict where the next cluster of infections might occur and take steps to prevent an outbreak. Still, as effective as this approach can be, conducting the necessary personal interviews requires considerable resources, says Haecker.

A more pragmatic approach may be to focus screening on people who have had repeated STDs. When Katherine Hsu, medical director of the Division of STD Prevention and HIV/AIDS for the Massachusetts Department of Public Health, examined all cases of syphilis, gonorrhea and chlamydia reported in her state from 2014 to 2016, she found that 6,999 people—just 0.14% of a population of almost five million people ages 13 to 65—accounted for more than one-quarter of STDs reported during those two years. (Names of those infected are routinely reported to health departments, to help them find and notify sexual partners.)

“We can identify people at high risk of getting and transmitting STDs by looking at how many previous STDs they’ve had,” says Hsu. Health systems have an opportunity to help control STDs in their communities by urging patients who have had multiple STDs to get screened every few months, she says. “Now we need some automated way, such as robo-texting, to get high-volume repeaters back to the clinics.”

There’s also an urgent need for quicker, easier STD screening. Someone who has been tested—in a clinic or using a home test for gonorrhea or chlamydia—may not get the results for a week or more, a delay that leaves time for additional sexual partners to be infected. A clinical trial is evaluating rapid screening tests that provide results in 20 minutes in a clinic. But Klausner wants instant, over-the-counter screening tests, similar to home pregnancy tests, that could speed the way to treatment. “There’s no scientific reason not to develop an over-the-counter STD test, just a lack of resources and political will,” says Klausner.

To combat congenital syphilis, all but six states require pregnant women to be screened for syphilis, and 14 states penalize clinicians who fail to test their patients. But screening for syphilis at the first prenatal visit, which most states require, misses women who are infected later in their pregnancies. And many women, including undocumented immigrants and those who use drugs or are homeless, shun prenatal care and are never screened—a problem that some health departments are trying to address. “Pregnant women who use drugs may feel judged or fear losing custody of their children if they seek prenatal care,” says Emalie Huriaux, STD program manager at Washington State Department of Health. “We can alleviate the stigma by screening these women where they are.”


Poster art by Orin Brecht

ONCE STDS ARE DIAGNOSED, treating syphilis and chlamydia is straightforward and effective. That’s not the case with gonorrhea. “It has developed resistance to every new antibiotic since the first sulfa drugs were introduced in the 1930s,” says Alabama’s Edward Hook, who studies new therapies for STDs and laments that the pharmaceutical industry shows little interest in developing new treatments. Even so, a few new classes of antibiotics are currently in clinical trials to test their effectiveness against gonorrhea.

One older drug—Cipro—may make a comeback. In 2007 the CDC advised against using the drug to treat gonorrhea because of increasing resistance. But according to research by Klausner at UCLA, 70% of gonorrhea in the United States still responds to Cipro, which is inexpensive and safe, and a rapid test he developed to identify whether a patient is likely to benefit is now in clinical trials.

Still, while effective diagnosis and treatment are essential, a vaccine to prevent STDs could make an even greater impact in reducing infection. But no research on a syphilis vaccine has ever advanced to a clinical trial, and trials for three gonorrhea vaccines have failed since the 1960s. To spur new research, the National Institutes of Health announced in 2018 it plans to award up to $9 million annually for five years to vaccine researchers, and even in advance of that support, the outlook has become more promising.

After people in New Zealand received a meningitis vaccine during an outbreak in the early 2000s, researchers noticed from medical records that teens and young adults who were vaccinated were 31% less likely to get gonorrhea than those who weren’t vaccinated. “The gonorrhea and meningitis organisms are closely related,” says Peter Rice, professor of medicine at University of Massachusetts Medical School in Worcester, who is in the late stages of developing his own gonorrhea vaccine. “GlaxoSmithKline, which makes the meningitis vaccine, is considering a clinical trial to evaluate whether its already proven vaccine is also effective against gonorrhea,” he says.

Chlamydia, meanwhile, poses other challenges. Unlike gonorrhea, which invades the body by attaching to cell surfaces and multiplying, chlamydia goes inside cells, where the pathogen hides as it replicates and produces inflammation. To neutralize chlamydia within the cells, an effective vaccine must create a robust T-cell immune response, a task that has been made easier in the past decade by the development of adjuvants—molecules that can be given with a vaccine to stimulate the immune system. Toni Darville in North Carolina is developing two chlamydia vaccine approaches—one that can be used intranasally and another that uses a disabled virus to deliver chlamydia antigens into cells. She says researchers are also anxiously awaiting published results from a Swedish clinical trial testing the safety of a novel chlamydia vaccine.

But even the most effective vaccines will need to be used, and vaccine researchers worry that the stigma of STDs and the country’s sexual mores will limit acceptance of a vaccine. Half of STDs occur in adolescents and young adults, so the target age for vaccination would be in the preteen and teenage years. And the experience with a very effective vaccine against the sexually transmitted human papillomavirus (HPV) is not encouraging. According to a 2016 CDC report, only half of 13- to 17-year-old girls and more than a third of boys have had the recommended two HPV vaccines to protect them from the virus, which can cause cancers of the cervix, vulva, vagina, penis and anus. “The HPV vaccine is amazing and lifesaving, but some parents are reluctant because they think giving it to their kids will lead to them having more sex, which isn’t the case,” says Darville.

Sexually transmitted diseases have plagued people for centuries and researchers seem undaunted in responding to today’s record-breaking numbers of cases. “We are now much more sophisticated in our understanding of these pathogens and how to control them than we were even a few decades ago,” says Kevin Ard at MGH. “I am optimistic about our ability to control STDs in the long term by combining tried-and-true approaches with new ones.