Scrub typhus, caused by the bacterium Orientia tsutsugamushi, affects an estimated million people globally each year, primarily across parts of Asia and the Pacific. Although the illness is treatable with antibiotics, it can become severe or even fatal if not diagnosed early.

One of its most puzzling features is the possibility of reinfection, suggesting that the body’s immune protection does not last.

In a new study published in Frontiers using a mouse model, scientists at The University of Texas Medical Branch (UTMB) compared how the immune system responds to two clinically relevant strains of the bacterium and found striking differences. One bacterial strain triggered strong, well-organized immune responses, allowing the body to control the infection and recover. The other strain caused widespread inflammation and disrupted key immune structures in the spleen that are essential for building long-term immunity.

This breakdown may help explain why protection after infection can fade quickly.

“Our findings show that not all strains of this bacterium behave the same way in the body,” said Dr. Lynn Soong, lead researcher and vice chair for research in the Department of Microbiology & Immunology at UTMB. “Some strains appear to modulate the immune system’s ability to form lasting protection, which is critical for preventing reinfection.”

The researchers also identified distinct immune “signatures” associated with severe disease, including heightened inflammatory responses and increased activity of certain immune cells linked to tissue damage. These insights may help scientists better predict which infections are likely to become severe and design therapies that reduce harmful inflammation.

Beyond its scientific implications, the research highlights an important public health message: Prior infection with scrub typhus may not guarantee long-term immunity. Prevention, early diagnosis, and timely treatment remain essential, particularly in regions where the disease is common.

The study represents an important step toward understanding how the body responds to scrub typhus and why those responses vary. Ultimately, the goal is to translate these findings into vaccines and treatments that provide stronger, longer-lasting protection.

Additional researchers in this study are Casey Gonzales, Joseph Thiriot, Hui Wang, Spencer Reiling, Dario Villacreses, Jiaren Sun, and Yuejin Liang.

Pictured at the top of the page: The map shows the Tsutsugamushi Triangle, a geographic region stretching across the Asia-Pacific where scrub typhus is traditionally endemic. The triangle covers an area of over 8 million square kilometers defined by three approximate points: Far-eastern Russia to the north; Pakistan and Afghanistan to the west, and Northern Australia to the south.