Humanized mice paves way for better typhoid fever treatment

New experiments in mice might reveal valuable clues for better treatment of typhoid fever in humans, says a new study.

A new model based on transplanting human immune stem cells from umbilicaly cord blood into mice that are susceptible to infections, could pave the way for better treating typhoid fever in humans.

Although mice are normally resistant to the dangerous strain of Salmonella that causes typhoid fever, the bacteria are able to reproduce in the mice that have received transplanted human cells.

The protection conferred by the present inoculation is short-lived, and doesn't have a booster effect, the researchers explained. The oral vaccine spoils easily if storage conditions aren't optimal - as is the case in many tropical countries where typhoid fever is common. It also requires multiple doses. Studies in travelers suggest that many fail to take the vaccine properly.

"The mouse Salmonella infection differs from human typhoid in a number of important respects," said Stephen J. Libby, research associate professor of laboratory medicine.

Fang added that Salmonella typhi, which causes human typhoid fever, has evolved many ways to evade infection-fighting defences inside humans. It can also enter and destroy disease-fighting cells. The bacteria induce inflammation where it is in their own self-interest, and suppress it when and where it might be a disadvantage, such as in the intestine.

Salmonella has changed over time by acquiring new DNA, such as plasmids and bacteriophages, from other organisms. This borrowed DNA makes it more virulent to humans and other animal hosts.

In the new study, researchers were also able to use the model to look for genetic factors that the typhoid bacteria need to cause severe illness. It could provide insights into how the human typhoid fever bacterium, Salmonella typhi, causes serious disease and to devise better strategies for the prevention of typhoid fever. Their research also demonstrates how mice engrafted with human stem cells can allow scientists to better understand human infections.

The study was reported recently in the Proceedings of the National Academy of Sciences.