A surveillance study of 10 US states shows the incidence of invasive group A Streptococcus (GAS) infection more than doubled from 2013 through 2022, researchers reported yesterday in JAMA.
The study, led by researchers from the Center for Disease Control and Prevention (CDC), analyzed clinical, demographic, and laboratory data on invasive GAS cases collected through the Active Bacterial Core (ABC) surveillance network, which covers nearly 35 million people across 10 states. While GAS is most widely known for causing noninvasive diseases such as strep throat and impetigo, it can also cause more severe and deadly invasive infections like sepsis, necrotizing fasciitis, and streptococcal toxic shock syndrome.
"What we're talking about here is a completely different beast, clinically," Joshua Osowicki, MBBS, PhD, a pediatric infectious diseases physician at Royal Children's Hospital Melbourne and co-author of an accompanying editorial, said in a JAMA podcast. "These cases really test, and often best, the most capable, high-tech hospitals in the world."
From 1995 to 2012, invasive GAS rates in the United States were fairly stable, ranging from 3.2 to 4.5 cases per 100,000 people, with cases disproportionately affecting adults 65 and over and nursing home residents. The authors of the study say that while that trend has continued, the substantial increase they found over the following decade reflects elevated incidence and outbreaks among groups that have been socially and economically marginalized.
Increases among drug users, homeless populations
From 2013 through 2022, surveillance in the 10 states (California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee) identified 21,312 cases of invasive GAS, with 20, 247 hospitalizations and 1,981 deaths. Bacteremic cellulitis (44.6%) was the most common syndrome, followed by septic shock (19.2%), bacteremia without focus (18.0%), and pneumonia (13.4%).
Among case-patients, 57.5% were men, 67.1% were White, 14.3% were Black, 5.6% were American Indian or Alaska Native, 2.5% were Asian, and less than 1% were Native Hawaiian or other Pacific Islander. The highest proportion of cases were in adults aged 18 to 64 years (63.7%), followed by adults 65 and older (30.4%) and children aged 0 to 17 years (6%).
Incidence of invasive GAS rose from 3.6 per 100,000 in 2013 to 8.2 per 100,000 in 2022. Incidence was highest among those 65 and older and increased from 9.1 to 15.2 per 100,000 (incidence rate ratio [IRR], 1.7; 95% confidence interval [CI], 1.5 to 1.9), but the relative increase over time was greatest among those aged 18 to 64 (3.2 to 8.7 per 100,000; IRR, 2.7; 95% CI, 2.4 to 2.9). The increase in invasive GAS incidence came despite significant decreases during the COVID-19 pandemic, when incidence fell by 73% among children younger than 18 and by 33% among adults 65 and older.
Although they comprised only 5.6% of cases, incidence rates among American Indian or Alaska Native adults (33.3 cases per 100,000) were more than 4 times higher than for White (7.7 per 100,000) and Black (7.2 per 100,000) adults and more than 10 times higher than for Asian adults (2.5 per 100,000).
Of the 19,515 case-patients with available data on substance abuse, the number of invasive GAS cases among people with documented injection drug use rose from 59 in 2013 to 515 in 2022. The number of cases among people experiencing homelessness increased from 52 in 2013 to 493 in 2022, and the estimated rate of invasive GAS cases increased from 85 to 806 per 100,000.
The percentage of adult patients with one or more underlying condition rose increased from 86.6% in 2013 to 93% in 2022. The most common underlying conditions were obesity (36.2%), smoking (33.4%), diabetes (29.9%), and acute skin breakdown (28.7%).
"An increasing prevalence of underlying health conditions associated with invasive GAS likely contributed to rising incidence," the study authors wrote.
The analysis also found rising levels of antibiotic resistance among invasive GAS isolates. While all streptococcal isolates were susceptible to beta-lactam antibiotics, tetracycline nonsusceptibility rose from 16.2% in 2013 to 45.1% in 2022, and the percentage of isolates that were nonsusceptible to both macrolides and clindamycin increased from 12.7% to 33.1%.
An alarming increase
In the accompanying editorial, Osowicki and Theresa Lamagni, MSc, PhD, of the United Kingdom Health Security Agency note that increases in invasive GAS have also been reported in other high-income countries, particularly in the immediate wake of COVID-19. But they say the scale and character of the increase in the United States is "particularly alarming" and "illuminates the extent to which invasive GAS thrives in settings of social disadvantage and marginalization." They also suggest that the increase in incidence might even be greater, since the ABC surveillance system doesn't include 8 of the 10 poorest US states.
"Overall, the theme of this US invasive GAS disease update looks to be a backward slide in the social determinants of invasive GAS, most evident in, but not limited to, disadvantaged and marginalized populations in the US," Osowicki and Lamagni wrote.
One of the contributing factors cited in both the study and the editorial is the substantial increase over the study period in the injection of illicitly manufactured fentanyl, which has a relatively short duration of effect and as a result is linked to more frequent injections and higher-risk injection practices, like sharing needles. That could also be contributing to increases observed in the homeless population.
Whatever is driving the increase in invasive GAS incidence, the study authors say it requires urgent attention.
"Efforts to reduce risk factors, including underlying skin breakdown and infections, particularly for groups with the highest disease incidence, will be critical to change the trajectory of invasive GAS infections in the US," they wrote.
In the JAMA podcast, Osowicki and Lamagni elaborated on what is needed to address the issue. While both agree that efforts should be made to address the underlying social disparities that appear to be playing a role in driving increased incidence, they say developing a vaccine should be a priority.
"It's one of those pathogens that causes a pandemic in plain sight, and because we haven't succeeded in controlling it, we look elsewhere for easier targets, but this is one of those hard targets that I think really need to commit to dealing with," Osowicki said.
"We absolutely, desperately need a vaccine for group A strep," said Lamagni.
