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PatientStormTracker shows that combined endothelial and epithelial barrier disruption of the colon may be a contributing factor to the Ebola sepsis-like syndrome

Ebola, Publications, Sepsis |

One key feature of Lyntek’s PatientStormTracker technology is its ability to provide insight into the patient’s evolving condition and signal new treatments of the condition through retrospective review.

In November 2014, Lyntek’s research team was asked by the MD PnP group to present PatientStormTracker to the White House Ebola response team and generate motion images of disease. While our team have seen many motion images of many different diseases, it did not take long to see that the reanimated motion images of Ebola virus infection are quite unique.

Ebola virus commonly produces an indolent viral syndrome with fever, vomiting, sore throat, headache and diarrhea. Although blood tests may indicate damage to cells of the liver or other organs, there may be few or no other abnormal laboratory findings, other than those explained by simple dehydration. In some cases, the viral syndrome is interrupted by a feared “Ebola sepsis-like syndrome” which progresses rapidly and is often fatal. Presently this Ebola sepsis-like syndrome is thought to represent an “out of control” immune response to the Ebola virus and its antigens.

When studying time-lapsed animations, I noted that while the viral syndrome progressed as viral load increased there was a marked disparity between the rise and peak of viral load and the Ebola sepsis-like syndrome. Some did not develop the sepsis-like syndrome at all, despite high viral loads. Another striking finding was that the viral syndrome caused by the Ebola virus and the sepsis-like syndrome often did not appear in the time-lapse motion images to exist on a continuum as one might expect if the sepsis-like syndrome was due to progressive stimulation of the inflammatory cascade by rising virus load. This could be explained by variations in relational regulation of the inflammatory response to the virus. However, even if the inflammatory response was initially depressed by the viral infection of immune cells, it seemed surprising that one would see such an explosive onset of the sepsis-like syndrome occurring superimposed on an indolent viral syndrome if they both comprised a response to viral antigens.

This observation raised an important point. What is the cause and trigger of the Ebola sepsis-like syndrome? When thinking about this question in dynamic terms, one observation of the time-lapsed pattern of the sepsis-like syndrome associated with Ebola virus infection stands out. The time pattern of the Ebola sepsis-like syndrome, reanimated in PatientStormTracker, looks exactly like some phenotypes of bacterial sepsis. Might the Ebola sepsis-like syndrome actually be a response to both viral and enteric antigens? Perhaps the Ebola sepsis-like syndrome is not of viral origin at all, but is actually caused by bacterial antigens which are “hijacked” by the virus and leaked into the blood vessels through selective barrier disruption in the colon to serve the interest of prolonging infectivity.

The theory that bacteria or endotoxin may translocate into the blood during severe sepsis is well-established. However, the pattern I was seeing was different. These subjects were not experiencing severe sepsis, only an indolent viral syndrome. Then they exhibited a clinical picture identical with bacterial sepsis, as if a “dam” holding back bacterial antigen had been suddenly breached.

Infection of human intestines is a successful trick of many pathogens that plague Africa. They use this mode of infection to readily enhance dispersion of their progenies into the environment for infection of the next host. The “selfish” genes of the Ebola virus may have developed a process of virulence extension, which allows the genome to divide longer at the expense of the host. By selectively infecting and breaking down the barriers of the colon, and allowing massive amounts of endotoxin to leak into the vasculatures, the virus may be essentially hijacking the antigens and toxins of the resident bacteria from the lumen of the colon to prolong its own survival. In so doing, the entire dying human is transformed into a new, alternative source of infection.

If this is true, a very simple treatment might be provided by having the patient drink a predefined volume of bowel preparation fluid and electrolytes, to flush out the colon while at the same time receiving hydration fluids. This could be provided with or without non-absorbable antibiotics. The treatment would be similar to the fluid normally given to flush the bowel out prior to colonoscopy, such as polyethylene glycol or sodium phosphate solutions. The patient would drink this at a predefined time after the onset of fever or upon the onset of diarrhea. This might be effective to flush the bacterial antigens and toxins from the colon before leaking into the blood vessels, mitigating the late Ebola sepsis-like syndrome. Of course, it is important to note that the treatment may have adverse consequences. Components from the bowel preparation fluid could leak into the vasculature. It could also increase exposure of others to diarrhea fluid if preparations are not made in advance to contain and decontaminate the stool which will be flushed from the colon.

At this point this treatment is still a hypothesis. However, it is possible that strategically timed consumption of mechanical bowel preparation fluid to flush out bacteria and endotoxin from the bowel might mitigate the late Ebola sepsis-like syndrome and provide time for the patient’s antibodies to clear the virus.

Lyntek’s PatientStormTracker technology analyzes and tracks the complex relational time patterns of clinical events, like the Ebola sepsis-like syndrome, and provides motion images of the patterned expression of disease. With this tool, researchers and clinicians will be able to better able to assess the physiologic progression of a condition and evaluate treatment options based on the apparent progression.

Read Dr. Lynn’s Letter to the Editor, published in Patient Safety in Surgery with detailed images and video, here. Text from this article also appears in a blog post published through BioMed Central on January 26, 2015, and can be found here.