Pandemic causes ‘mass disruptions’ in STD field
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For 5 straight years, the United States hit record highs in reported cases of chlamydia, gonorrhea and syphilis.
Preliminary data indicate that 2019 will be the sixth straight record-breaking year for STDs, although the CDC has extended the deadline for local health authorities to submit their STD reports because of the COVID-19 pandemic.
Source: Courtesy of National Coalition of STD Directors
Based on available data — which were presented by Hillard Weinstock, MD, MPH, chief of surveillance and data in the CDC’s Division of STD Prevention, during a roundtable discussion for journalists in September at the STD Prevention Conference — there were an estimated 1.76 million cases of chlamydia, 602,000 cases of gonorrhea and 123,000 cases of syphilis reported last year in the U.S., with a 20% increase in syphilis cases among newborns. These are increases compared with 2018, when 1.75 million, 583,405 and 115,045 cases were reported for the three infections, respectively.
According to Weinstock, the increases continued into 2020, with reported cases in the first 2 months of the year surpassing 2019 levels, but “that changed by early March.” Compared with the same period in 2019, reported cases of chlamydia, gonorrhea and syphilis were down 53%, 33% and 33%, respectively, in the spring this year, due mostly to pandemic-related declines in testing.
Weinstock said that because the data for both years are still being compiled, with 2019’s data not expected to be fully available until April 2021, “the decrease may be underestimated.”
The pandemic also has caused shifts in resources that have impacted progress in developing vaccines and treatments. Infectious Disease News spoke with experts about the pandemic’s impact on the fight against STDs and about other emerging issues in the field.
‘Mass disruptions’
In April, the National Coalition of STD Directors (NCSD) began to examine the effect that the response to COVID-19 has had — and will likely continue to have — on the country’s STD programs and specialists.
“The NCSD was seeing mass disruptions to the STD field. We were getting calls and emails from our members, the jurisdictions funded by the CDC to carry out STD public health work, telling us they had been redirected to their state’s COVID-19 emergency response,” NCSD Executive Director David C. Harvey, MSW, told Infectious Disease News.
“There was no coordination, no national effort, no extra funding, no clear communication. Everyone was in a state of chaos,” Harvey said. “We stepped up to support our members, share resources, and advocate for them and their work.”
According to the NCSD, a survey distributed to STD program directors in 65 CDC-funded jurisdictions and an NCSD network of 1,100 disease intervention specialists revealed that the public health response to STDs had been interrupted, and attention and manpower had been diverted to the COVID-19 response.
Specifically, responses to the survey showed that 78% of people in the STD/HIV health department workforce are or have been redeployed to the COVID-19 emergency response for any period of time. Additionally, 20% of STD directors reported that their STD program operations were completely disrupted and unable to complete core functions
In St. Louis, only 8% of STD and HIV sites operated without changes at the height of lockdown restrictions, according to data presented during the STD conference in September by Hilary E.L. Reno, MD, PhD, an associate professor of medicine at Washington University School of Medicine in St. Louis. Reno and colleagues estimated that testing for chlamydia and gonorrhea in the city fell 45% and that 5,000 HIV tests were missed.
“We’re not back to pre-COVID times. I think patients are still having trouble,” Reno said during the conference. “Either they’re needing to go to work, or they’ve still got their kids at home and it’s harder to get out and get testing, but we’re at least back to two-thirds of that volume.”
Harvey said that 31% of STD programs in the U.S. were leading their state or city’s COVID-19 contact tracing efforts.
“The STD field is full of contact tracing expertise,” Harvey noted. “STD program directors, STD epidemiologists, and especially disease intervention specialists know how to stop the spread of infection. They know how to find people, make them feel comfortable, educate them, elicit partners and contacts. This expertise and the public health response to STDs continue to be an example of how contact tracing should be done.”
Additional data revealed that 98% of STD programs were relying on phone calls and text messaging to reach clients for STD, HIV, and/or COVID-19 interviews.
Despite the challenges presented by COVID-19, experts agreed that it is possible to mitigate STD increases through commitment and innovation.
Vaccine development
Currently, the only effective STD vaccines available protect against HPV, hepatitis A and hepatitis B. However, according to Christopher S. Hall, MD, MS, AAHIVS, an HIV care physician and chairman of the NCSD Clinic+ Clinical Advisory Committee, other vaccines are under development, including vaccines for HIV and HSV.
“For these two diseases, development of effective vaccines has been elusive, though there is a promising herpes simplex vaccine in preclinical development,” Hall told Infectious Disease News. “In addition, there is early testing of a vaccine for gonorrhea, along with evaluations to determine whether other existing vaccines, such as those that prevent meningococcal disease, might be effective in preventing gonorrhea, since these two organisms are related biologically.”
Infectious Disease News Editorial Board Member Jeanne M. Marrazzo, MD, MPH, director of the University of Alabama at Birmingham division of infectious diseases, is the principal investigator for a study that received a $10 million NIH grant to assess the efficacy of the meningitis vaccine Bexsero (GlaxoSmithKline) to protect against gonorrhea.
“The pandemic has created unprecedented demand for many of the platforms, including reagents and collection materials, that comprise the bulk of nucleic acid amplification testing (NAAT) for STIs worldwide — particularly gonorrhea and chlamydia,” Marrazzo said. “Because testing for these infections is pivotal to numerous clinical trials that are either studying them as primary outcomes or need to know whether they’re present to treat them, this has posed a really big challenge for STI researchers as well as direct care providers.”
Marrazzo said the Bexsero study has not yet started but is “poised to do so.”
“At least one of our sites is having to work through alternative supply channels to procure an adequate supply of NAATs for the STI testing we need to screen potential participants,” she said.
Carlos del Rio, MD, Infectious Disease News Editorial Board Member and executive associate dean at the Emory University School of Medicine, called the recent discovery that meningococcal serogroup B outer membrane vesicle vaccines could induce moderate protection against gonorrhea “the most exciting news” in the search for a vaccine for gonorrhea.”
Unfortunately, del Rio said, “there is little to no progress in a vaccine against chlamydia or syphilis.”
New guidelines
Increasing resistance to frontline gonorrhea treatments — some strains are resistant to multiple antibiotics — has raised concerns, leading to calls for new treatments.
Cephalosporins remain the last effective class of antibiotics against gonorrhea, for which the CDC currently recommends a single 250 mg dose of intramuscular ceftriaxone and 1 g of oral azithromycin.
“New CDC STD treatment guidelines” — which will be published in 2021 — “are likely going to change the recommended therapy,” del Rio said. “One of the most exciting things is the possibility of more directed therapy.”
In a recently published study in Clinical Infectious Diseases, Jeffrey D. Klausner, MD, MPH, professor of infectious diseases at the David Geffen School of Medicine at the University of California, Los Angeles, and colleagues tested directed therapy of ciprofloxacin in patients with untreated gonorrhea.
They used a genotypic PCR assay to assess the patients for a genetic mutation that is the “main mechanism that renders ciprofloxacin” — once recommended as a first-line therapy for gonorrhea — “ineffective against Neisseria gonorrhoeae.”
They then tested the efficacy of a single 500 mg oral dose of ciprofloxacin in patients with culture-positive gonorrhea who did not possess the mutation. According to the study, ciprofloxacin was 100% effective in treating gonorrhea in all 106 participants who lacked the mutation (95% 1-sided CI, 97.5%-100%).
Genotyping like this “could have substantial medical and public health benefits in settings where the majority of gonococcal infections are ciprofloxacin susceptible,” Klausner and colleagues wrote.
Another treatment option in development for drug-resistant gonorrhea is zoliflodacin, a first-in-class oral antibiotic. Entasis began enrolling patients last year in a phase 3 trial of oral zoliflodacin for the treatment of uncomplicated gonorrhea that is being run by the Global Antibiotic Research and Development Partnership (GARDP).
According to GARDP, the phase 3 trial was initiated in the U.S. in September 2019 and is now actively recruiting patients, although it, too, has been affected by COVID-19. Recruitment was temporarily paused in March because of the pandemic “but has recommenced and continues to make progress,” GARDP officials told Infectious Disease News.
Additionally, the first patient in the Netherlands was enrolled in June, and there are plans to open additional clinical trial sites in South Africa and Thailand, GARDP said. The partnership said it was too premature to provide timelines for results from the trial.
“However, a preplanned data safety monitoring board review was conducted in March 2020, and although both Entasis and GARDP remain blinded to the assessment, it was recommended that they continue the trial without modification,” GARDP said.
As for syphilis and chlamydia, del Rio said the topline treatment options are still holding up — although he said clinicians are “moving back” to using doxycycline for chlamydia rather than azithromycin, which is still “slightly” favored in CDC guidelines, as the agency puts it.
Other STDs
Chlamydia, gonorrhea and syphilis are the only major nationally notifiable STDs in the U.S. but not the only clinically important ones.
“In STD care, we are always on the alert for emerging infections,” Hall said. “In recent years, clinicians became accustomed to seeing lymphogranuloma venereum, a more aggressive variant of chlamydia, and developed greater proficiency in clinical recognition of this disease despite the absence of an FDA-cleared test for this organism.”
Clinicians also have been challenged by the emergence of Mycoplasma genitalium, which can cause urethritis in men and cervicitis in women. If left untreated, it can also cause pelvic inflammatory disease in women, leading to chronic pelvic pain, ectopic pregnancy and infertility.
Hall noted that an FDA-cleared test was not available for M. genitalium until 2019. According to the CDC, few antibiotics are available to treat it.
“With testing still uncommon, prevalence is uncertain, but studies of STD clinic populations suggest 15% or more of patients may be affected,” Hall said. “Recognition relies on clinical judgment and testing where available, and treatment can be extremely challenging, requiring multiple backup regimens for infections that fail initial therapy.”
According to the CDC, resistance to azithromycin, which has been recommended for treatment of M. genitalium, is high around the world. The agency said it is collaborating with other groups on research to better understand the prevalence of M. genitalium in the U.S. and how it develops resistance.
Prevention
Researchers continue to study antimicrobial PrEP for STDs — specifically, using doxycycline for chlamydia. Del Rio called the use of doxycycline for STD PrEP “clearly beneficial.”
“The findings from several studies have shown promise for doxycycline to reduce syphilis, chlamydia and gonorrhea but better studies are needed,” the CDC told Infectious Disease News. “Several large randomized controlled studies are underway to more definitively answer this question. It will also be important to better understand the impact of antimicrobial PrEP on the microbiome and the development of resistance of STIs and other commensal bacteria.”
Hall said doxycycline is being evaluated to prevent syphilis in at least one ongoing major study of HIV-positive and HIV-negative men who have sex with men who experienced at least one STD in the prior year.
“Since doxycycline treats both syphilis and chlamydia, it might be effective in preventing both these STDs,” he said. “However, doxycycline only incompletely treats gonorrhea, so the worry is that it could worsen drug resistance in this important organism in individuals using doxycycline to prevent other STDs.”
Behavioral interventions to reduce risk factors for STDs do not appear to have been very useful, del Rio said.
“Just look at how STDs are going up,” he said.
Harvey said the most effective tools are routine screening, prompt treatment and contact tracing.
“Contact tracing is crucial to any infectious disease response, and disease intervention specialists are the experts,” he said. “They know how to complete a source and spread analysis, how to conduct a network analysis, and how to plot and track exposures. They also know motivational interviewing techniques, and they often come from the communities they serve. These partner services or contact tracing tools are what is needed when responding to COVID-19 as well as to STDs.”
- References:
- Klausner JD, et al. Clin Infect Dis. 2020;doi:10.1093/cid/ciaa596.
- National Coalition of STD Directors. COVID-19 & the state of the STD field: Phase II. https://www.ncsddc.org/resource/covid-19-the-state-of-the-std-field-phase-ii/. Accessed on Oct. 19, 2020.
- Reno HEL, et al. Impact of COVID-19 on STD services. Presented at: STD Prevention Conference; Sept. 14-24, 2020 (virtual meeting).
- For more information:
- Carlos del Rio, MD, can be reached at cdelrio@emory.edu.
- David Harvey, MSW, can be reached at info@ncsddc.org.
- Christopher S. Hall, MD, MS, AAHIVS, can be reached at info@ncssddc.org.
- Jeanne M. Marrazzo, MD, MPH, can be reached at jmarrazzo@uabmc.edu.
- Hilary E.L. Reno, MD, PhD, can be reached at hreno@wustl.edu.
- Hillard Weinstock, MD, MPH, can be reached at media@cdc.gov.
Click here to read the At Issue, “Is casual sex a risk factor for SARS-CoV-2 transmission?”
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