The STDs Infectious Disease Experts Hate Most

There are dozens of sexually transmitted infections and diseases (STIs/STDs), running the gamut from A for asymptomatic chlamydia to Z for Zika. Here’s a poser. If you could magically erase any sexually transmitted infection or disease instantly, which one would you choose?

Michelle Collins-Ogle, MD, who spent 20 years as medical director of a dedicated HIV clinic, let out a little groan at having to decide, but took only a moment: “gonorrhea.”

That was also the top choice for Ina Park, MD, associate professor at University of California San Francisco School of Medicine; medical director of the California Prevention Training Center; and author of Strange Bedfellows: Adventures in the Science, History, and Surprising Secrets of STDs.

And, “gonorrhea,” says David Aronoff, MD, director of the Division of Infectious Diseases in the Department of Medicine at Vanderbilt University Medical Center.

On any given day in 2018, according to the Centers for Disease Control and Prevention (CDC), 1 in 5 individuals had an STI. Gonorrhea actually comes a low fifth on the CDC’s list of STI prevalence, but the number of cases had recently jumped 63% in only 4 years.1

April happens to be the CDC’s STD Awareness Month2 and the reason these infectious disease experts worry most about gonorrhea is primarily because of the fear that it’s becoming resistant to all antibiotics. “I need gonorrhea to go away before we won’t be able to treat it,” Collins-Ogle says. “So if I could wipe it off the face of the earth, I would.”

Aronoff classes it with those infections that “we thought we had control over—but then lost control. Gonorrhea is increasingly hard to treat, and increasingly easy to spread.”

A photomicrograph of a gram-stained specimen demonstrating the presence of gram-negative diplococci, indicative of gonorrhea infection.

We may be running out of time to stop it. “We’re down to 1 class of antibiotics left to treat it, and while there are a few others in the pipeline being studied in clinical trials, none is quite ready for prime time,” Park explains. In December 2020, she notes, the CDC modified its guidelines, which used to recommend dual treatment with ceftriaxone and azithromycin as first-line therapy for gonorrhea. Due to concerns over increasing antibiotic-resistance as well as stewardship, azithromycin was removed, and the dose of ceftriaxone was doubled.

“In the few cases of multidrug-resistant gonorrhea that failed all conventional therapies,” Park says, “patients had to be hospitalized and treated with broad spectrum IV antibiotics such as ertapenem. We really don’t want to have to resort to that for an infection as common as gonorrhea.”

Eliminating Gonorrhea

Collins-Ogle, who’s now an assistant professor of pediatric infectious disease at Albert Einstein College of Medicine and an attending pediatrician for infectious diseases and adolescent medicine at Children’s Hospital at Montefiore, has a second reason for wanting to rid the world of gonorrhea: what happens when it’s untreated. “Gonorrhea is no joke,” she says. “It causes really harmful sequelae when it’s not treated. And complications of gonorrhea are more serious in women who aren’t treated. Women get [pelvic inflammatory disease] very easily. They can have scarring, they can have sterility. Genital gonococcal ophthalmia in newborns. It’s just a horrible bacterium.”

With gonorrhea gone, what would rise to No. 2 on the list?

Syphilis.

After a near disappearance in the US in 1999-2000, Park says, “Syphilis has come back with a vengeance, and one of the biggest concerns I have is over the resurgence of congenital syphilis.” Indeed, according to the CDC’s 2018 STD surveillance report, cases of primary and secondary syphilis rose 71% between 2014 and 2018, and congenital syphilis cases increased dramatically, by 185%.1

“Syphilis, to me, is the most fascinating STI we have,” says Collins-Ogle. “It sort of quieted down, but then when its resurgence occurred, it occurred in a demographic we hadn’t seen before. The last time we saw syphilis rear its head it was in the ’80s, with pregnant women and newborns born to mothers who weren’t treated. Now we’re seeing it in men who have sex with men (MSM), particularly young men of color.”

This resurgence is completely different than in the 1980s to 1990s, she says, in part because of changes in screening. “I would say that because we had the resurgence of syphilis then, [obstetrician-gynecologists] did a better job of screening women for syphilis. And we all made sure that babies were tested as well, so I think we did a better job of screening, diagnosing, and treating in that demographic. But we didn’t see it coming when it happened in MSM.”

Screening is better now. “Now,” she says, “if you get diagnosed with HIV, you get screened for everything else. Or if you get an STI, you get syphilis or gonorrhea, chlamydia, you automatically—well, we don’t do a good job universally—but you should be screened for HIV.”

However, “I just saw a young guy a couple weeks ago who had gone to an emergency [department] with symptoms consistent with an STI. He got tested for STIs but he didn’t get an HIV test. So he came to our center and asked for an HIV test. We’re still not doing a good job of making those connections in that demographic.”

The problem is, we’re also still not doing a great job of emphasizing prevention, Collins-Ogle says. “Our health care system and education system lag behind reality and what’s happening in the real world. We lag in our understanding of even how to speak to the various demographics and how to educate them. It’s all of that, kind of wrapped into why we continue to see these epidemics the way we do.”

And the right messages aren’t getting to the right people. For instance, 30 years or so after the worst of the AIDS epidemic, “We still have a lack of understanding about the role of condom use,” Collins-Ogle says. “I keep telling people, if only they’d use condoms, we wouldn’t have this problem with HIV.”

Messaging Problem

Moreover, the messages aren’t targeted enough. “We’re taking one message and assuming that it’s well received and understood among all demographics—and it’s not. For example, for men in their 50s and 60s, their understanding of condom use was to prevent pregnancy. For women who are older, the purpose for having condoms was to prevent pregnancy, not STIs. And now we’re trying to tell young people that condoms are used to prevent STIs and can prevent pregnancies.” In other words, we’re trying to make one message fit all circumstances.

Age, culture, and education all make a difference. The issue, Collins-Ogle emphasizes, is that we aren’t talking about sex, and we aren’t talking about it in a comprehensive way, “to reach all the different ways people have sex. There’s no sex [education] for MSM, there’s no sex ed for lesbians, gay women, there’s no sex ed for bisexual people.” Depending on where you live, you’re going to get a different message about how infections are spread and how to prevent them, she says. “I find out from my young male patients: They don’t know how to use a condom! Nobody ever showed them how! I’m not kidding you.”

STI/STDs are a threat to all humans, but nearly half of new STIs in 2018 were in the age group of 15 to 24 years.1 “We’ve failed at making sure we’ve adequately prepared these kids to be safe,” Collins-Ogle says. “They don’t know, they’re only going by what they’re told by other people or what they’ve read online.”

One method of reaching them might be to use the social media they’re most comfortable with, as investigators in a 2019 study did.3 They found that MSM who used sex-seeking social media platforms were more likely to share HIV information than those who were mostly on generic platforms. This echoes what Collins-Ogle is fervent about: People are more willing to ask for help and receive help in a nonjudgmental, accepting environment.

Even with effective screening, treatment, and education, STIs can be like movie villains who just won’t die, who change form, and who keep coming back to wreak havoc. There are some bright spots, though. Syphilis is still very susceptible to penicillin, Collins-Ogle points out. And Park says, “We already have a fantastic vaccine against [human papillomavirus].” What’s more, she adds, “We’ve managed to nearly eliminate mother-to-child transmission of HIV in the [United States] through aggressive screening and treatment. But we also need to mobilize around reducing morbidity and mortality around congenital syphilis, [which] is preventable with screening and prompt treatment during pregnancy.”

Several drugs for gonorrhea have been studied, or are being studied in clinical trials, Park says, including zoliflodacin, closthioamide, gepotidacin, and solithromycin. “There’s also a very interesting study going on in the United States and Thailand looking at the meningococcal group B vaccine (which prevents against Neisseria meningitidis) that induces antibodies that may also protect against Neisseria gonorrhoeae. These are, however, still earlier-stage clinical trials.”

No Vaccines

But why on earth can’t we get a vaccine for any of these infections and diseases? In short, “it’s complicated,” says Aronoff. “To get vaccines into trial you need unlimited money, interest in the disease, participants for the trials—and lots of disease.” All of those components were in place for coronavirus disease 2019, which is why vaccines could zip through (relatively speaking) to public distribution.

Also, he notes, “Some diseases lend themselves to vaccines. It’s incredibly hard to arm the immune system against HIV, malaria, tuberculosis, because they all have a different relationship to the immune system than do diseases that we’ve been able to develop vaccines for, like measles and smallpox. A complicated virus like HIV, for instance, integrates into the DNA.”

Which probably explains why Operation Warp Speed has not yet been translated into STI/STD vaccine research. “Operation Warp Speed had a $12 billion-plus price tag,” Park says. “If that much was poured into STI vaccine research, I’m sure we’d be much further along with various STI vaccine candidates than we currently are.”

Effective treatments may be on the way, but in the meantime, good reliable data are critical, especially when infections attack in packs. “Back in the ’80s, we didn’t have a direct correlation between STIs and AIDS,” says Collins-Ogle. “Now we know having syphilis predisposes you to HIV acquisition. We also know having herpes simplex virus [type] 2 predisposes you to HIV. When we started seeing syphilis in gay men it wasn’t necessarily equated to HIV. At that time, they weren’t going hand in hand. Now we definitely know they’re a couple. I think that may be why syphilis caught us off guard with men and HIV. We didn’t have the data to make that link.”

The resurgent STIs seem to be stronger than before, but in the last several years, the CDC has “embraced bigger, faster, stronger countermeasures” like the Sexually Transmitted Disease Surveillance Network (SSuN).4

SSuN, a collaboration of state, county, and city health department sentinel sites, allows health care providers to access and use updated, specific data to monitor and track rates for several STDs simultaneously. The “timely data snapshots,” as the CDC calls them, give users a comparison group for trends; if gonorrhea rates go up in one location, for instance, a public health expert can use the SSuN data to determine whether it’s a local or broader trend.

The surveillance system integrates data across multiple diseases. For instance, SSuN data offer an extensive breakdown of HIV co-infection rates among people diagnosed with gonorrhea or seeking care in STD clinics. Moreover, SSuN provides complete demographic, clinical, and behavioral information, helping clinicians and investigators monitor and combat emerging antibiotic resistance.

A Continual Battle

The ongoing fight to eradicate (or at least prevent, or at the very least control) STIs is a little reminiscent of the story of poor Sisyphus, doomed to push a massive rock uphill, whereupon it would roll back down again…and again, eternally. But there are successes, both in treatments and encouraging behavior change. As intractable as gonorrhea and syphilis can be, targeted public health campaigns can help.

In Alaska, for instance, cases of early syphilis had spiked from 24 to 97 between 2017 and 2018—a 300% increase. The Alaska Division of Public Health (ADHP) teamed up with the CDC’s Division of STD Prevention to build a relationship with the community, in particular with MSM. ADPH organized testing and community outreach events, and by January 2019, more than 300 people had been screened for syphilis.5

And Hawaii is taking a layered approach. The state is a critical site for monitoring antibiotic-resistant gonorrhea (resistance historically emerges in the East and moves into the mainland United States through Hawaii). Participating in the Gonococcal Isolate Surveillance Project to collect samples of N gonorrhoeae, Hawaii’s STD clinics collect a higher percentage of samples for monitoring resistance than in any other state. When test results from 7 patients at the Hawaii State Department of Health’s STD clinic showed possible resistance to both drugs in the last recommended treatment, local public health professionals acted quickly, handing off the information to the “next link in the chain,” disease intervention specialists (DIS). The DIS made sure the 7 patients were cured by the treatment they received, and also began contact tracing to prevent spread of the potentially resistant strain. Within a matter of weeks, all but 1 of the patients were tested (and retreated in 1 case).4

The Sisyphus tale is usually considered a metaphor for futility. Still, one theory holds that it’s a metaphor for the sun rising and setting. And rising again. Certainly STIs can be relentless. But so is science. By winning battle after battle, we may win the war.

JAN DYER is a writer and editor specializing in clinical topics. She lives in Suffern, New York.

References

1. Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2018. Accessed February 28, 2021. https://www.cdc.gov/std/stats18/default.htm
2. Centers for Disease Control and Prevention. STD awareness month; CDC digital toolkit. Accessed March 2, 2021. https://www.cdc.gov/std/sam/STDAwarenessMonthToolkit.pdf
3. Durvasula M, Pan SW, Ong JJ, et al. Enhancing public health messaging: Discrete-choice experiment evidence on the design of HIV testing messages in China. Med Decis Making. 2019;39(5):568-582. doi: 10.1177/0272989X19859344
4. Centers for Disease Control and Prevention. Shedding light on disease in the US: how STD prevention programs benefit from strong data. Accessed February 28, 2021. https://www.cdc.gov/std/products/success/SSuN-Success-Story_FINAL.pdf
5. Centers for Disease Control and Prevention. Sexually transmitted diseases; STD prevention success stories. Accessed February 28, 2021. https://www.cdc.gov/std/products/success/default.htm