How genomic sequences could battle drug-resistant STIs

Several common sexually transmitted infections, including syphilis and gonorrhea, have long been treated with antibiotics — but overuse and misuse of that very treatment have fueled antimicrobial resistance in recent years as the diseases evolve defenses against the drugs. Antimicrobial resistance kills an estimated 700,000 people per year, and if not contained, is predicted to cause up to 10 million deaths each year by 2050. In particular, resistance to antibiotics is growing rapidly in cases of Neisseria gonorrhoeae, which has continued to avert all of the first-line antimicrobial drugs introduced to treat it over the past 90 years, earning it the nickname “super gonorrhea.” This has led to concerns that in the future, the bacteria — which can cause infertility, inflammation, increased vulnerability to HIV, and blindness in newborn babies — could become untreatable. The African continent currently bears a “disproportionate share” of the global burden of gonorrhea cases, according to the World Health Organization. According to WHO, data on drug-resistant gonorrhea predominantly comes from higher-income countries, and data from lower-income countries is “exceedingly scarce,” leading the agency to surmise that documented reports are “​​only the tip of the global health burden.” Leveraging the use of genomic sequencing technology to monitor this drug resistance is crucial, said Deborah Williamson, director of microbiology at Royal Melbourne Hospital, during a presentation at the IAS Conference on HIV Science this week. After a sample is collected from a patient with an STI, researchers can use genome sequencing to analyze the genetic code of the pathogen, comparing it to other pathogens circulating globally. This can help researchers track antimicrobial resistance and thus contain outbreaks of drug-resistant STI strains. This technology is now being used at an unprecedented scale to better understand the COVID-19 outbreak and to track new variants of the virus. But it’s not commonly used on STIs, Williamson said. “Although we've got the [genomics] technology, we might not have the resources to fully implement it.” --— Deborah Williamson, director of microbiology, Royal Melbourne Hospital “Rates of established STIs are really approaching levels we haven't seen in decades. Genome sequencing is this powerful tool that we have now that can monitor the emergence and spread of infections, including STI across the globe,” she said. “Responsible use of genomic technologies may enable targeting public health interventions.” But expanding access to genomic testing — an expensive and complicated process — can be a challenge in low-resource settings, she said. Targeted health responses Aggregate numbers and trend lines around increased STI cases actually tell the public health community little about the spread of antimicrobial resistance and the forces driving outbreaks of STIs, said Williamson, who advocates combining epidemiological information, including information collected by health workers — such as age, gender, zip code, and travel history — with genomic sequences, which can show that a strain of a pathogen is drug-resistant, she said. “When you integrate those two data sets, you can start to untangle some of the complex epidemiological behavioral factors that drive transmission. And that's when you can have precision interventions to interrupt transmission,” she said. Her team in Melbourne did a series of local studies marrying those data sets. In one of their studies, her team sequenced samples of the Shigella bacteria, which causes the infection shigellosis, which leads to diarrhea, fever, and stomach cramps. It is spread through contact with feces, which can happen during sexual activity. The researchers coupled this data with data collected by health authorities and found that many cases were linked to returning travelers. They also identified high levels of antibiotic resistance in the strains they identified of certain communities of men who have sex with men. The resistance was spread by a gene that was present on a piece of DNA, called a plasmid, that can transfer between different strains and species of Shigella. “This is a perfect storm: We've got these dense transmission networks, we've got a pathogen that is highly infectious, and a mobile plasma mediating drug resistance,” she said. One hypothesis from her team is that the overuse of the antibiotic azithromycin to treat many STIs is fueling this resistance and is leaving relatively few treatment options for Shigella in some parts of the world. And the problem of drug-resistant strains spreading goes far beyond the management of STIs. She added that there is concern that this plasma could spread to other pathogens like E. coli or salmonella, which could “really open up the spectrum of diseases and would really cause a major public health problem.” Genomic sequencing is easier to perform on some STIs than others. For example, syphilis bacteria is considered extremely difficult to work within the laboratory and thus is more expensive to analyze this way. Limited access, competing priorities Before COVID-19, genomic sequencing was mostly used in retrospective analyses of outbreaks, Williamson said. But the pandemic catalyzed the use of the technology as part of real-time public health response, as in the widespread worldwide monitoring of the delta variant. The same could be done for STIs. With such a tool, forecasters could predict where new clusters of infections might arise, allowing for early shutdowns of outbreaks and information on whether they are associated with a particular group of people or a specific venue. That, in turn, could allow for public health messaging better tailored to those individuals, with efforts to improve access to testing and treatment. But the ways in which samples are collected also impact whether a genomic sequence can be performed, she said. For example, many health workers have moved away from culturing the bacteria of Shigella or gonorrhea cases, and instead use a polymerase chain reaction diagnosis, which doesn’t allow for genomic sequencing. The urgency around the COVID-19 pandemic has catalyzed the building up of this infrastructure in many low- and middle-income countries, including the launch of the Africa Pathogen Genomics Initiative. But whether STIs are sequenced regularly depends on the priorities of local public health authorities, she said. In many places, diagnostic services are still elementary, meaning genomic sequencing — which is next level — is not prioritized when resources are limited, she added. “I think STI [are an area] where we haven't yet shown the real-time public health benefit of using genomics,” she said. “There's a danger there that, although we've got the technology, we might not have the resources to fully implement it.” Visit the Building Back Health series for more coverage on how we can build back health systems that are more effective, equitable, and preventive. You can join the conversation using the hashtag #BuildingBackBetter.