Historically, shigellosis cases in the United States have primarily been seen in young children in daycare settings and in people who’ve traveled to countries with poor sanitation. Infections with Shigella, a gut pathogen that causes diarrhea and vomiting, have also been fairly easy to treat.

But the profile of who’s most at risk of shigellosis is changing, and the infections is becoming much harder to treat, according to a report published last week in Morbidity and Mortality Weekly Report, the flagship publication of the Centers for Disease Control and Prevention (CDC).

In the report, researchers from the CDC and health departments across the country revealed that the vast majority of US Shigella infections from 2011 through 2023 were in adult men, a high proportion of whom (47%) had HIV. Analysis of nearly 17,000 Shigella isolates found that the proportion of isolates considered extensively drug-resistant (XDR) rose from 0% during 2011-2015 to 8.5% in 2023. 

Approximately one-third of patients were hospitalized. And among patients with travel history, more than 80% reported no recent international travel.

The report’s corresponding author said the findings reflect changes in epidemiology and resistance that are transforming Shigella from a primarily self-limiting infection that rarely required antibiotics into an emerging public health threat with limited treatment options. 

“Together, it’s a very concerning pattern of XDR Shigella strains that are being seen among vulnerable populations,” Naeemah Logan, MD, an epidemiologist with the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, told CIDRAP News.

And it’s a pattern that is increasingly being seen by US clinicians and researchers. Shangxin Yang, PhD, who directs the Molecular Microbiology and Pathogen Genomics Laboratory at the University of California Los Angeles (UCLA) Health, said clinicians at the hospital identified one local case of XDR Shigella in 2022. Since then they’ve seen roughly one case a month.

“It’s almost like an explosion of this pathogen in the community,” Yang said.

Limited treatment options

Ferric Fang, MD, and his colleagues in the Seattle area have also been watching these trends emerge up close. According to the CDC, an estimated 450,000 Americans get shigellosis each year. And while most people with the disease usually get better with fluids and rest, some cases are more severe, Fang said.

“About 15% or 20% of our patients who present with Shigella end up admitted to the hospital. They’re dehydrated. They have dysentery,” said Fang, a professor at the University of Washington School of Medicine and director of the Harborview Medical Center’s Clinical Microbiological Laboratory. And there are few options to treat the patients infected with XDR strains. The isolates tested by the CDC were resistant to five oral antibiotics.

The CDC report notes that oral carbapenems, pivmecillinam, and fosfomycin may be effective. But none have been approved by the Food and Drug Administration for shigellosis. “Treatment of XDR shigellosis remains challenging because no optimal therapy has been established,” the report states.

“Clinicians who are encountering these infections are really relying on scant anecdotal data” in terms of managing their patient, Fang said. Yang said that clinicians at UCLA Health are seeing success with fosfomycin, both in terms of resolving the infection and eradicating Shigella from stool, but they don’t have enough data yet.

It’s a very concerning pattern of XDR Shigella strains that are being seen among vulnerable populations.

“It’s based on very limited cases, so we can’t generalize this statement,” he said.

Fang said that while he welcomes the report, he’d like to see more focus on the at-risk groups. Although the most common ways people get shigellosis are from eating or drinking food and water that’s been contaminated by feces or being in contact with someone who is or has been sick with Shigella, sexual activity is becoming an increasingly common mode of transmission. Fang and Yang said many of the cases of XDR Shigella seen in their hospitals are in men who have sex with men (MSM).

“We’ve known for decades that there are a number of enteric pathogens that can be sexually transmitted almost exclusively between men who have sex with men,” Fang said. But Shigella “falls through the cracks in public health between sexually transmitted infections and foodborne infections,” he added. And in cases of XDR Shigella seen at hospitals, data on sexual activity aren’t always captured.

“I think a lot of men who have sex with men don’t realize that it’s sexually transmitted,” he said.

The CDC tracks antibiotic resistance in Shigella through the National Antimicrobial Resistance Monitoring System, which is the primary surveillance system for foodborne pathogens. But the agency has highlighted sexual activity as one mode of transmission. And Logan noted that while the researchers did not have enough data on sexual behavior to “make any meaningful interpretations,” data from other countries suggest XDR strains are spreading through sexual networks. 

In March, the United Kingdom’s Health Security Agency reported a sharp increase in sexually transmitted shigellosis, primarily in MSM. More than half of the infections caused by one species of the bacterium—Shigella sonnei—were XDR.

“This is by no means unique to the US, but really part of a broader global pattern,” Logan said.

Threat of wider spread

Another at-risk group is people who have unstable housing or are homeless. Fang said that, in Seattle, Shigella infections in the unhoused took off in the early months of the COVID-19 pandemic, when public restroom facilities were closed and the city’s unhoused population had no place to use the bathroom or wash their hands. People were drinking water from ornamental fountains and defecating out in the open, Fang said.

“This made them very vulnerable to a lot of infectious agents, not just Shigella, but Shigella is one of the ones that makes [people] sick enough to come into the emergency department,” Fang said. “I would say we see more Shigella in persons experiencing homelessness than we do in any other at-risk population.”

One reason is because Shigella is so easily transmitted, with as few as 10 organisms required to transmit the infection, Logan explained. “What makes it really challenging is that it has this remarkable knack for targeting really vulnerable populations,” she said.

I would say we see more Shigella in persons experiencing homelessness than we do in any other at-risk population.

And now there’s concern that XDR Shigella could spread to a broader population. In January, Yang and researchers from the UCLA’s David Geffen School of Medicine reported a novel XDR strain detected in two patients with no epidemiologic links—they lived 80 miles apart and their hospitals visits didn’t overlap. One was a cancer patient who “did not fit any of the risk factors,” Yang said.

Yang said it would be “scary” if XDR strains become a more frequent cause of foodborne illness and spread beyond at-risk populations. “Having such resistant bacteria that is also highly contagious in the community is never a good thing.”

Fang said that, going forward, he would like to see the CDC move beyond data collection and start investigating specific patterns of XDR Shigella transmission and exploring new methods of surveillance and prevention.

“We need more innovative approaches to try to control it,” he said.