It was their last normal day. Rory woke up in the middle of the night complaining of sharp pains in his leg, and then threw up. The next morning, his stomach was tender and he had a high fever. His worried parents got him to a pediatrician and then shuttled him to an emergency room. In both places, staff diagnosed a stomach bug. Back at home, his temperature kept climbing, despite the Tylenol his parents gave him. He was restless and unable to eat, and his skin looked mottled. One day after he left the ER, his parents took him back. This time, the diagnosis was different. Bloodwork and Rory’s other symptoms showed he had a profound bloodstream infection, and was sliding into septic shock. He died in the intensive care unit two days after being admitted. “It was so fast,” Orlaith Staunton remembers. “We could not understand what had killed such a healthy child in just a couple of days.” The pathogen that attacked Rory and sent him into sepsis, an overwhelming immune-system response to infection, was group A streptococcus, bacteria that cause strep throat and live on skin and in the throat lining. It’s the same pathogen that has killed 19 children and teens in the United Kingdom in the past few weeks during a brutal wave of strep infections. One of the mysteries of that outbreak is why the UK has been hit so hard, and why the US—much larger and with a more fragmented health care system—has not. The answer may be awareness: The story of Rory Staunton’s death inspired legislation, was written up in journals, and is taught in medical schools. Or the answer may be data—or possibly a data gap. The US has no connected system that can gather infection reports in real time the way the UK’s system can. And that could mean cases have been missed. A tiny note posted to the website of the US Centers for Disease Control and Prevention last week—”CDC is looking into a possible increase in invasive group A strep infections among children in the United States”—suggests something is going on here as well. The outbreak in the UK—7,750 cases and 16 deaths in England, according to the UK Health Security Agency—has been attributed to scarlet fever, a complication of group A strep infection that combines the painful swallowing and high fever of strep throat with a raised, inflamed rash, a reaction to toxins the bacteria produce. On light-colored skin, the rash is bright scarlet. (It can be hard to detect the color on dark skin, but the rough bumpiness can be felt.) Scarlet fever is a reportable illness in the British health system: When diagnosed in an adult or child, the case is flagged in its information system and aggregated into national data. That’s not the case in the US. “It’s one of the challenges we have, that so much in the US goes unreported,” says Anthony Flores, a physician-scientist who researches streptococcus and is chief of pediatric infectious diseases at UTHealth Houston. “Anecdotally, we hear that cases exist, but we just don’t know what the number of cases is in the US right now.” Similar regulations followed in Illinois in 2016 and New Jersey in 2018, inspired by sepsis cases in those states. In 2019, a study in JAMA showed the regulations worked. New York sepsis deaths were 3 percent lower than they would have been without the protocols in place. There are no such regulations, and no similar level of awareness, in the UK. “This was completely not on people’s radar until two weeks ago,” says Simon Clarke, a microbiologist and associate professor at the University of Reading’s School of Biological Sciences. “Most people, I think, had never heard of it.” At best, scarlet fever might feel like a shared cultural memory. It was a common cause of death in childhood before antibiotics arrived in the 1940s, and the horror of its rapid attack and long-lasting complications are threaded through classic children’s literature. Scarlet fever almost kills saintly Beth March in Little Women, published in 1868; her slow wasting and death afterward may be due to the infection damaging her heart. It blinds Mary Ingalls, the oldest daughter in the Little House books, in a story set in 1879. And in The Velveteen Rabbit, published in 1922, scarlet fever sickens the boy who owns the rabbit toy, and leads to the stuffed bunny becoming real. (When the family doctor orders all the boy’s toys to be burned to disinfect his room, a fairy saves the bunny from the pile of discards and transforms him.) But scarlet fever never went away—and in places that count their cases, its occurrence has been rising fitfully since the 2000s. Cases began to rise in Singapore in 2006 and in South Korea in 2008. In 2011, cases in China and Hong Kong suddenly soared fourfold. Beginning in 2014, England saw a rise in cases to levels that had not been seen in 50 years, followed by a second spike in the winter of 2017-18 that exceeded those levels. And then in 2018, scarlet fever cases in Germany rose above what had already occurred in England and Hong Kong. It’s that backdrop of cases—rising to historic heights with no clear explanation why—that reinforces the alarm over scarlet fever now. The World Health Organization said last week that the health ministries of France, Ireland, the Netherlands, Sweden, and the UK have all reported further spikes in cases. On the same day, the UK Health Security Agency said the current cases are three times what they were at the same point during the 2017-18 spike. British news is full of reports of huge local case counts—35 times the expected average just in Wales—with schools closing in Devon and Yorkshire and pharmacists reporting antibiotic shortages. The program also doesn’t cover the whole country, but draws from what the agency considers a representative subset of the US. For group A strep, that includes counties surrounding Atlanta, Baltimore, Denver, Portland, San Francisco, and in parts of Tennessee and upstate New York, as well as the entire states of Connecticut, Minnesota and New Mexico—all together, about 34.6 million people, or about 10 percent of the US population. That system represents a keyhole view, and its analysis lags behind events. Right now, though, the “CDC is hearing anecdotes from some US doctors of a possible increase in iGAS infections among children in the United States and is investigating this increase,” Scott Pelley, an agency spokesperson, wrote to WIRED by email. Plus, last week, the widely read infectious-disease newsletter ProMEDMail posted a report that the state of Minnesota (widely considered to have one of the best public health data systems) saw twice as many invasive cases in November as it did a year earlier. At the end of the week, NBC News reported that children’s hospitals in Arizona, Colorado, Texas, and Washington were seeing spikes as well. The question for both the US and UK is why scarlet fever, as well as the invasive forms of group A strep infection, are hitting so hard right now. Sequencing done in the UK shows there has been no abrupt change in the bacteria. “So if it’s not the bug that’s changed, it has to be something in us,” Clarke says. Lockdowns and a slowdown in social mixing, both of which were observed more strictly in the UK compared to the US, would have deprived children of their normal brushes with strep bacteria. Now that life has returned essentially to normal, all those kids are being exposed at once—and just as influenza and RSV have surged into that immunity gap, strep infection may be doing the same. Those other infections also could open the door for strep: “Concurrent or preceding viral infections such as influenza, and skin conditions such as chickenpox, may increase risk for iGAS infections,” the CDC’s Pelley said by email. But in the UK, scarlet fever usually intensifies later in the winter season, in February as opposed to November. It is possible that depriving the bacteria of its usual hosts yanked its epidemiology off-track; the same thing happened to RSV, which usually occurs in winter but in 2021 bounced down the calendar all over the world. The question posed by scarlet fever now is whether its usual peak has merely arrived early, or whether it will continue its onslaught all the way through its normal season in spring. “We don’t know what’s going to happen in January, February, March,” Clarke points out. The conundrum of what’s causing the UK surge—and whether it will also happen in the US—drives home the need for better, faster data about how the disease moves. That’s a goal for Flores, who oversees a unique collection of group A strep isolates gathered over more than a decade from hospitals within the enormous Texas Medical Center. The collection is smaller than the CDC’s but more comprehensive, because it contains samples from people who passed through clinics and emergency rooms as well as hospital stays, and also retains all their clinical details. The collection provides a broader picture of which bacterial strains are circulating locally and what kind of illness they are causing. Earlier this year, Flores’ group applied whole-genome sequencing to it to identify chains of transmission of group A strep in Houston. Their analysis provides a model for how a rapid prediction system could receive samples, detect hot spots, and point out where the disease might intensify next. “Our dream is to be able to do this type of survey, not just for group A strep but for other pathogens, almost in real time,” he says.
