Typhoid fever is an ancient scourge that remains all too deadly in the developing world today. And while it has been described in detail for more than a century, the reasons for its lethality have never been understood.
Yale researchers now have an answer.
The disease's most fatal complication, perforation of the small intestine, appears late in the illness and remains deadly even after antibiotics are administered. Why the intestine fails has always been a mystery. In a study published in Nature Microbiology, the laboratory of Jorge E. Galán at Yale School of Medicine (YSM) reports that typhoid toxin, circulating in the bloodstream, damages blood vessels of the small intestine, leaving them unable to withstand the later arrival of the bacteria.
Intestinal perforation, it turns out, is a disease of blood vessels.
"This is a problem solved," said Galán, the Lucille B. Markey Professor of Microbiology and Professor of Cell Biology at YSM. The new research completes a series of findings that the Galán laboratory has assembled since discovering typhoid toxin in Salmonella Typhi two decades ago.
Typhoid fever complications - including neurological disease occurring with almost no bacteria in the bloodstream and perforation confined to the lower small intestine - have a common origin: the toxin which impacts the lining of blood vessels and reaches different vascular beds, which are networks of small blood vessels which supply blood to the body . Other features of the illness, including the characteristic loss of circulating white blood cells, are also driven by the toxin, the researchers say.
