November 10,2014
A World War One British soldier – long after his death – may provide clues to finding new treatments and a possible vaccine for dysentery. The disease continues to be a major problem in developing countries due to unsanitary conditions and conflict.
The Lancet medical journal has published a special World War One edition to mark the 100th anniversary of -- what was once called -- the “war to end all wars.” It reports on research being done to reconstruct the complex genome of the Shigella flexneri bacterium that causes dysentery.
Dr. Kate Baker -- of the Wellcome Trust Sanger Institute -- is the first author of a new study. She said, “Today, bacillary-dysentery, which is caused by Shigella, still kills thousands of people. Typically these are children in developing nations. They’re in the age group less than five years old.”
It remains a problem, she said, despite all the scientific advances since the early 1900s.
“Actually, in World War One there was a historical analysis that identified the main factors that caused the outbreaks. Those problems are still problems today. The first two were hygiene and malnutrition, and the last one was a lack of specific therapies. And we still don’t have a licensed vaccine for Shigella. Advances in bacteriological diagnosis were not available in World War One. But now we have them, and we can sequence the genome of this bacterium. But it’s really just showed us how it’s changed over time to evolve against our efforts to control it.”
And a vaccine remains elusive.
Baker said, “It’s difficult to vaccinate for Shigella for a number of reasons. Firstly, there’s not a very good animal model for Shigella. We find it difficult to reproduce disease in any animal model. So, testing a vaccine for Shigella has to be done usually in human volunteers, which, as you can understand, is more difficult.”
Another problem is that Shigella has many similarities with the common e-coli bacterium. It lives in the human gut. So, vaccinating against Shigella could have adverse effects on other bacteria that are good for us. There are many strains of
e coli and a few have been in the news for causing sometimes fatal infections.
“The last reason it’s difficult to vaccinate against dysentery,” she said, “it’s a very diverse pathogen. There are over 16 serotypes of Shigella flexneri. So finding a single protein that we can use as a vaccine target is quite difficult.”
Dysentery is still treated as it has been for many years, mostly fluids and bed rest – and the use of antibiotics in severe cases.
Dr. Baker said researchers hope to find clues to dysentery by studying a veteran who died of the disease in France in 19 15 – Private Ernest Cable of the Second Battalion of the East Surrey Regiment.
“We went back to the First World War intentionally because of the hundred year centenary because we wanted to commemorate the deaths of soldiers during that time – particularly those that were from infectious disease. But actually this is a disease that – as we said – is really important today. And the isolate itself is a historical one. And it’s actually the first isolate of Shigella that’s available.”
The isolate is an actual sample of the bacterium taken from Cable’s blood in 19 15 and preserved all these years at the National Collection of Type Cultures in England. It basically started the process of storing bacteria and viruses for future research. And this was done long before antibiotics were widely available.
“Penicillin wasn’t discovered until 1928/ 1929 and it wasn’t used clinically until the 1940s. And so they weren’t really thinking about antibiotic resistance at the time. But the microbiologist, who preserved this sample, really did show great foresight because actually they said that the war had brought together a great diversity of these different types of Shigella flexneri – this [bacterium] that causes dysentery. And they intentionally preserved it. They said, we’re not going to see this again and we need to preserve this diversity so we can study it,” she said.
Baker added that researchers are gaining insight into why dysentery has been so difficult to tackle for the past 100-years. The sample shows that Shigella has become increasingly drug resistant. It is difficult to sequence its DNA, so no new treatments or vaccines will be immediately available. But scientists are looking for parts of the bacterium genome that have remained the same and may offer stable targets for drugs or a vaccine.