The next time your teenager complains, “But when am I ever going to use this?”, referring to math they are learning in school, now you can reply, “Septicemia!”
As we know, septicemia occurs when bacteria enter the bloodstream from an infected organ or site, and despite many methods designed to reduce the spread of infections, fighting infections with antibiotics once they occur, and other supportive therapies, septicemia, or a resultant sepsis, remains a leading cause of death in hospitals. Could mathematics help us solve this problem?
Well, the University of Michigan School of Medicine is researching mathematical approaches that may become a powerful ally in hunting down and destroying the bacteria that cause septicemia. Using complex mathematical techniques that model bacteria behavior in the bloodstream, scientists may be able to offer a mechanical approach to help rid the body of bacteria, which would be a welcome addition to our declining list of effective antibiotics.
From the story released by the University of Michigan:
John Younger M.D., M.S., and his team have more research to do before their models yield results that might affect human treatment. But already, they are seeing the potential for how to improve the models and use them to simulate different aspects of human bacteremia and sepsis.
“We’re trying to understand the rules for how bacteria traffic in the bloodstream – and if you understand the timing of those events you might be able to better understand how best to detect the bloodstream infection when it’s present,” he says. “We’re also working on ways to fundamentally change the rules of engagement between the bacteria and the host. There are mechanical features at play in terms of getting these bacteria in flowing blood out. If we can change the mechanics of that interaction, then we can potentially have a therapy that the bacteria don’t really have an opportunity to defend against or develop resistance against. And that could be a useful therapy.”
The new findings give more information than ever before about how bacteria act within the blood vessels of the body, and how they might be filtered out of the blood and into organs where the immune system can attack and kill them.
Now, this model of how bacteremia occurs in “real world” of the fast-moving bloodstream – rather than a placid Petri dish or test tube – can be put to work to study how best to combat or prevent bacteria in the blood.
Better treatment for bacteremia and sepsis, then, might include strategies that can help the body filter bacteria out of the bloodstream and into these areas.
In the paper published in Shock, Younger and his team describe their new model of bacterial infection of the blood and organs, which they validated through experiments in mice.
The model combines the physiology of a blood vessel, the fluid dynamics of blood, and math-based models of how bacteria multiply and move between the bloodstream and organs. It also allows the researchers to better understand different conditions – including a low-immunity state such as what a cancer patient might experience, and a higher-than-usual blood flow rate that is often seen in patients who are fighting off a severe bloodstream infection.
While creating the model, the researchers tested it by seeing how well it matched real-life mouse infections. Using bacteria that had been modified to give off a weak light signal that can be detected from outside the body, and other bacteria that could be detected through blood tests, they could see where the bacteria concentrated in the body during different stages of the infection, and how quickly they were killed and cleared from the body.
The liver, lung and spleen had the highest concentrations, and the lung appeared to have the most effective bacteria-killing system.
Some of the mice were given a chemotherapy drug that is often used in cancer patients – one that kills white blood cells. Cancer patients and intensive-care unit patients are especially prone to bloodstream infections not only because of their weakened immune systems, but also because they often have long-term intravenous catheters that allow medicines to be given directly into the bloodstream.
While this helps patients avoid repeated intravenous needles, it also gives bacteria an easy pathway straight into the blood.
Indeed, the mice that received the chemo drug and an injection of bacteria all died of an out-of-control bacterial infection, while mice that didn’t receive the drug were able to clear the infection from their bloodstream. The model successfully showed the same outcome.
An important part of bloodstream infections associated with catheters is the clumping-together of bacteria on surfaces – which is also seen in urinary catheters that cause many thousands of infections each year. But clumping that occurs within the bloodstream itself is also important since it may help bacteria become more vulnerable to immune system response.
The paper in the Bulletin of Mathematical Biology describes a model of this process – known as flocculation – and sets the stage for further study of treatments that might accelerate clumping or make the clumps more stable. That, in turn, might help the body fight off infection more effectively.
Press release: Battling bacteria in the blood: Researchers tackle deadly infections
UPDATE: Thanks to our thoughtful reader Tim: we stand corrected! We changed the word sepsis for septicemia, as it is indeed the proper term. Thanks, again, Tim!