Typhoid fever ranks among the oldest illnesses on record, yet one puzzle has refused to give way: why does the small intestine of certain gravely ill patients split open, frequently late in the disease and even once antibiotics are under way? A team at Yale has now put forward an answer. That dreaded complication, they say, is fundamentally a disorder of the blood vessels.
Reporting in Nature Microbiology, the group headed by microbiologist Jorge Galan points the finger at the organism so-called typhoid toxin. Made by the bacterium Salmonella Typhi, it travels through the bloodstream and harms the thin lining of tiny vessels along the gut. By the time the bacteria themselves show up in strength, those softened vessels give way, bringing bleeding and, eventually, rupture clustered at the Peyer patches, pockets of immune tissue in the intestinal wall.
The advance hinged on a fresh laboratory model. Since the germ ordinarily makes only people ill, the characteristic bowel damage had never before been recreated in mice. The scientists exposed the animals to the toxin first and infected them by mouth only afterwards, and it was that order of events that left normally resistant mice vulnerable.
Galan, who identified the toxin some twenty years ago, describes the matter as settled. In his account the same poison links wildly different sides of the disease, from nerve damage with barely any bacteria in the blood to the telltale fall in white cell counts. The crucial point, he says, is not a microbe fanning out across the body but one toxin reaching one vascular bed after another.
The work also opens doors on treatment. Researchers can at last trial toxin-blocking antibodies, vaccines and vessel-protecting medicines against the very complication behind most deaths from the disease, used side by side with the antibiotics that clear the bug. Typhoid is still blamed for roughly 200,000 deaths each year, overwhelmingly where vaccines and solid care are in short supply, and it falls hardest on the old and the young.
