British scientists have discovered a vaccine that creates an immunity to Traveller's Diarrhoea - the global curse with a handful of names, but one certain unpleasant effect on businessmen and holidaymakers alike who venture far from their native lands.
A team of scientists from the UK has had a breakthrough in its decade-long search for a vaccine to prevent one of the top travellers' nightmares - Delhi belly.
The Cambridge University bioengineers have spent the past 10 years working to create the vaccine which could help some of the millions of people who contract it every year. The illness, which is the most common among travellers, is caused by bacteria usually ingested in feacal-contaminated food or water.
The scientists' research has been made more difficult by the body's own efficient defence mechanisms. The main problem has been finding a way to transport the living bacteria to the lymph nodes without them being killed by natural defences such as saliva and bile.
Now that the scientists have come up with a solution, it's only a matter of time before the vaccine comes on to the market. The disease is usually caused by a strain of Escherichia coli, or E-coli and the side effects are loose stools, abdominal cramps, nausea and bloating.
Working with the biotechnology company Prokarium, based in the UK, Professor Nigel Slater, head of the university's department of chemical engineering and biotechnology, and Krishnaa Mahbubani, a postdoctoral research associate, have found a way of transporting specific bacteria to the gut that stimulates the immune system into producing a defence against typhoid and the most common bacteria that causes Delhi belly. It involves using an ingredient which binds itself to the bile to prevent it from killing the bacteria.
"This is a new way of delivering vaccines. The idea is that you can deliver vaccines through the wall of the intestine and into the lymph nodes, and that creates an immunity," says Prof Slater, speaking to The National from his office at Cambridge University.
To do this, the team had to first identify a so-called friendly bacteria that could be transported to the intestine and used by the body to create immunity.
But the crux of the work lay in finding a way to prevent the body's digestive system from destroying this friendly bacteria before it had a chance to do its job.
As a natural protection against ingested bacteria, the enzymes in saliva and the corrosive acid in the stomach are effective, but problematic when it comes to keeping bacteria alive.
There was also the issue of storage and supply as the team was determined to produce a vaccine that didn't require an injection.
"What we are really after is a vaccine that can be distributed around the world, is very easy to take and is very stable so that you can be sure it can be kept for long periods of time and stays active," Prof Slater says.
"We don't want to depend on a cold supply chain, dependent on it always being refrigerated. If the vaccine, from the minute it's made right through to being administered, always had to be stored at plus-four or minus 20 [degrees Celsius], it's quite an inconvenience."
Traveller's Diarrhoea (TD), its more official name, is certainly not a new illness but there is still little a traveller can do to protect themselves in advance besides trying to build up a natural immunity.
The illness has probably been around for as long as people have travelled, but the title Montezuma's Revenge - named after an emperor of Mexico who ruled from 1502 to 1520, during which time the Spanish conquered the Aztec empire - has a more modern, comic intent.
The revenge aspect supposedly refers to the hostile attitudes of countries that were previously colonised by stronger neighbours, but are now reaping their revenge in the form of this unpleasant sickness. Not that Montezuma has the monopoly when it comes to having the last laugh.
Other euphemisms include the Cairo Two-Step, Mummy's Tummy, Pharaoh's Revenge and of course Delhi belly.
According to the Centres for Disease Control and Prevention in the United States, about 10 million people develop it every year - accounting for between 20 and 50 per cent of all international travellers. It lists Latin America, Africa, the Middle East and Asia as particularly high-risk destinations.
The main cause is bacterial organisms which cause diseases of the intestines. These account for 80 per cent of cases.
The most common of the organisms is enterotoxigenic Escherichia coli, known as Etec, or a strain of E-coli, which is responsible for up to 75 per cent of TD cases. Other common bacterial causes include Shigell and Salmonella.
The basis for the new vaccine is actually a strain of inactivated Salmonella which can carry the proteins from the bacteria that cause TD.
"We have a strain of salmonella that has been naturally selected to remove the toxic gene; it's a safe form of Salmonella," explains Prof Slater.
That particular pathogen is also responsible for typhoid fever, so the vaccine offers dual protection against Etec and the fever. The formula has already undergone clinical trials in India, Prof Slater says, and was found to be effective when administered as a single dose.
"The biggest problem was all the people that have had these trials, they would be given a glass of bicarbonate solution, the purpose of that was to neutralise the Ph in the stomach ... then they consume a glass with the bacteria liquid. That's not a very convenient way of dosing.
"And bacteria would have to be chilled to be distributed in that way. Nobody knows really what happens to this bacteria as they go from mouth down into the intestine. It's a long journey. They have to go through a low Ph in the stomach and survive the bile. How many living ones you get down into the intestine is a bit of a mystery."
The scientists worked out that drying the bacteria was the best way to keep them alive on the journey, but this didn't offer a whole solution. Packaging them in capsule form can protect the dried microbes against saliva, and a special coating can protect it in the stomach, but once it reaches the small intestine it then faces the alkaline bile.
When dried, the bacteria loses its natural defence against bile and rehydrating it in the presence of bile will also kill it.
"When you dry them, you don't kill them. They are just in a state of suspended animation. As soon as it gets rehydrated they come back to life," explains Mahbubani.
"The drying of the bacteria isn't a new technology. What's interesting is the fact nobody has managed to get it to the small intestine without killing it off while they rehydrate."
The solution lies in Bile Acid Resins (Bars), which are also used to treat cholesterol and bind the bile to keep it away from the bacteria while they rehydrate. This is the breakthrough the team have been searching for.
"The whole object was to get away from injections," says Prof Slater. "If you imagine giving mass inoculations, it's a vast number of needles.
"Whereas with a tablet or capsule, once it's made it's as simple as handing it to somebody.
"There really is two categories of market. There's the market for travellers, business travellers. If you're going to Delhi you could have one of these and you would be safer. There's also mass immunisation in the Third World countries. For both markets you need this characteristic of having something that's very stable and you can store."
The clinical trials have already tested the safety and efficacy of the vaccine, so the next trials, due to begin later this year, should be something of a formality and a final check.
"It almost is there for typhoid. We have now reconstructed it to give immunity against Etec, so we are starting these clinical trials knowing the organism is safe."
The original goal of the project was to create an HIV vaccine, but the scientists weren't able find a protein sequence that was strong enough to safely elicit HIV immunity.
"It's been really interesting and exciting to go from very pure engineering to something that's an application of engineering," Mahbubani says, "to actually say something you are working on in pure science, is to become a product that is going to make a difference."