Some people infected with pathogens spread their germs to others while remaining symptom-free themselves. Now, investigators at the Stanford University School of Medicine believe they may know why.

When the scientists gave oral antibiotics to mice infected with Salmonella typhimurium, a bacterial cause of food poisoning, a small minority — so called “superspreaders” that had been shedding high numbers of salmonella in their feces for weeks — remained healthy; they were unaffected by either the disease or the antibiotic. The rest of the mice got sicker instead of better and, oddly, started shedding like superspreaders. The findings point to a reason for superspreaders’ ability to remain asymptomatic. They also pose ominous questions about the widespread, routine use of sub-therapeutic doses of antibiotics in livestock.

About 80 percent of all antibiotics used in the United States are given to livestock — mainly cattle, pigs and chickens — because doing so increases the animals’ growth rates. Experts have already voiced concerns about how this practice contributes to the rise of drug-resistant pathogens. But the new study, published online Oct. 20 in Proceedings of the National Academy of Sciences, highlights an entirely different concern.

“We’ve shown that the immune state of an infected mouse given antibiotics can dictate how sick that mouse gets and also carries implications for disease transmission,” said Denise Monack, PhD, associate professor of microbiology and immunology and the study’s senior author. “If this holds true for livestock as well — and I think it will — it would have obvious public health implications. We need to think about the possibility that we’re not only selecting for antibiotic-resistant microbes, but also impairing the health of our livestock and increasing the spread of contagious pathogens among them and us.”

Upon invading the gut, S. typhimurium produces a powerful inflammation-inducing endotoxin, which annually results in an estimated 1 million cases of food poisoning, 19,000 hospitalizations and nearly 400 deaths in the United States. Passed from one individual to the next via fecal-oral transmission, it is known to produce a curious pattern of pathology among infected individuals: Some 70-90 percent of those infected shed fairly light amounts of bacteria (and so are not very contagious). But the remaining 10-30 percent — superspreaders — remain symptom-free yet shed huge amounts of bacteria, causing the great bulk of the pathogen’s spread through a population. The reasons for this dichotomy have not been understood.

Evading detection

From a public health standpoint, knowing how to easily and quickly identify superspreaders could help curtail or even prevent epidemics, Monack said. Yet superspreaders don’t appear to be sick, so they evade treatment. At the moment, the only way to determine which category a person or beast belongs to is by inspecting each individual’s stool, a procedure that would be inconvenient at best even with livestock.

But the Stanford team has discovered that the immune systems of superspreaders and non-superspreaders are in differing states, raising the possibility of a blood test that could make identifying superspreaders more practical.

Salmonella infection in mice is not uncommon, said Monack. “Mice in a barn can be infected with salmonella for a long time and not get sick. They run around perfectly healthy. They’re happy little incubators for salmonella.”