Science & Research

Unravelling the secrets of septic shock

Research team tackles leading cause of ICU deaths

Dr. Spencer Gibson
Dr. Jude Uzonna

BY JOEL SCHLESINGER
Winnipeg Health Region
Wave, May / June 2011

Most people have heard of toxic shock, a catastrophic condition in which a blood infection causes the body's organs to shut down.

Also referred to as septic shock, it's one of the leading causes of deaths in our intensive care units, says Dr. Jude Uzonna, Associate Professor of Immunology at the University of Manitoba's Faculty of Medicine. In fact, during the 2009 H1N1 pandemic, many of the fatalities were actually caused by septic shock.

It's long been known that septic shock results from a bacterial blood infection that runs rampant when the body's immune system fails to eliminate the invader from the blood.

But Uzonna, a 2010 Manitoba Research Chair award recipient, and his team of researchers are studying a hypothesis that suggests the cause of septic shock is actually the other way around.

"Our working model is that septic shock results from excessive and unregulated immune response to blood pathogen - like using a sledge hammer to kill a fly where you also cause collateral tissue damage in the process," Uzonna says.

Central to their focus is the role of a special type of immune cells known as regulatory T-cells that control the magnitude of how the body's immune system fights infections. "Their job is to knock other immune cells on the head and thereby dampen or prevent them from going haywire and initiating excessive and deleterious immune response," he says.

The results of the research so far have supported their theory. Tests have demonstrated that mice die very quickly when these regulatory cells are taken away from their system because they lose the ability to regulate their immune response even when injected with bacterial products that normally do them no harm.

Uzonna says they're still trying to understand whether it's a lack of regulatory T-cells that leads to septic shock or whether they simply stop working. The results of the research could lead to better care for patients in ICUs, and even help reduce deaths in future influenza pandemics.

In the future, Uzonna says treatment for sepsis/ septic shock could be similar to platelet transfusion for patients with clotting disorders. "We could forsee a situation where a patient with septicaemia receives a transfusion of regulatory T-cells," he says.

For Uzonna, however, his research at the Department of Immunology doesn't just involve understanding toxic shock. He is also leading research into treatment for parasitic diseases that affect millions of people in some of the world's poorest regions.

Leishmaniasis is a single-celled organism that is spread by sand flies found in South America, Africa, the Middle East and Asia, and infects more than two million people a year. "But I can tell you this is a gross understatement because the disease affects very poor countries and very poor people," he says. "Most people, when they get sick, they don't go to the hospital."

Depending on the species of the parasite, leishmaniasis can cause death or leave its hosts with disfiguring scars. While medication to treat the disease - also known as dum-dum fever - has been available since the 1940s, it has not been effective. Not only is it expensive, but its toxic nature can lead to fatalities in some instances.

Uzonna and his research team have been studying how to genetically manipulate the organism. They are developing an attenuated parasite that doesn't cause illness but can still infect people. Much like a vaccine containing a virus that doesn't cause illness, the attenuated parasite would prime a person's immune system to quickly recognize and destroy future infections by Leishmania parasites. So far, he has signed a memorandum of understanding to test his vaccine on monkeys, who also are also susceptible to infection, at the Institute for Primate Research in Nairobi, Kenya.

Uzonna, who studied veterinary medicine in his home country of Nigeria, is also involved in researching a vaccine for another parasite, only this time to save cattle. In fact, this parasitic infection, which is widespread in his homeland, is the reason he became involved in parasitic and immunologic research in the first place.

African trypanosomiasis is commonly known as sleeping sickness. It's a curable disease that affects the brains of those it infects, making them sleepy "zombies" and is fatal if left untreated.

Uzonna wants to uncover why this parasite is so virulent in exotic cattle imported to Africa.

"It's the number one problem that prevents rearing cattle in a lot of African countries because the hybrid European and North American breeds of cattle do not survive in those areas," he says. The indigenous cattle are too small to be commercially viable. "Solving the problem in cattle will not solve the problem of human disease, but it will have a huge economic impact." And that, in turn, will help improve living conditions among some of the poorest regions of the world, he says.

Joel Schlesinger is a Winnipeg writer

Wave: May / June 2011

About Wave

Wave is published six times a year by the Winnipeg Health Region in cooperation with the Winnipeg Free Press. It is available at newsstands, hospitals and clinics throughout Winnipeg, as well as McNally Robinson Books.

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