So-called ‘traveller’s tummy’, or galloping diarrhoea, afflicts as many as half of those who travel to foreign parts. While this statistic is worrisome enough, it masks an even deeper issue, which is that doctors, in developing countries particularly, are very prone to reaching for antibiotics as their first port of call to treat any foreigner who turns up in their surgery with traveller’s tummy.
The problem with this is that the world is finding that antibiotics have been prescribed so freely to both humans and livestock, for a whole range of conditions, that we are in danger of finding ourselves with none, or very few, effective antibiotics in the very near future.
A world without antibiotics would also be a world where no one would dare to do bowel surgery, and transplants of all kinds would be impossible. There is also the not-altogether irrelevant fact that antibiotics are not particularly useful if the cause of the diarrhoea is viral or fungal, rather than down to bacteria. Antibiotics have no efficacy in the case of viral infections, unless the virus has weakened the individual’s resistance to the point where a bacterial infection has also developed.
So, as Professor Colin Garner, Chief Executive of the charity Antibiotic Research UK notes, the fact that antibiotics are routinely prescribed for cases of traveller’s tummy in China, for example, is seriously worrying. Antibiotic Research UK recently teamed up with Dr David Brown, the Co- Inventor of Viagra and a prolific and enthusiastic seeker of new drugs and non-microbial cures, in order to support his latest project, which aims to provide a non-antibiotic cure for traveller’s tummy.
An age-old problem
The project, which Dr Brown is in the process of seeking to put through a pilot human trial in China, involves an innovative cure based on three cheap and easy-to-obtain ingredients. These three ingredients, says Dr Brown, work together to boost the human immune system in a way that none of the three can singularly achieve. The result, he hopes, will be a very fast acting cure for traveller’s tummy that does not rely on antibiotics.
But first, it is worth considering the scale of the challenge that diarrhoea poses to the medical profession. As Professor Garner notes, and as we have already highlighted, diarrhoea is multi-factorial as far as its causes are concerned. It can be caused by bacteria, by a reaction to unfamiliar spices and foods, or the cause can be viral or even fungal. What is common to all forms of severe diarrhoea … is the speed with which sufferers can become dehydrated, which poses its own dangers.
What is common to all forms of severe diarrhoea, however, is the speed with which sufferers can become dehydrated, which poses its own dangers
“This is an age-old problem and a lot of work has been done on it over the years, but it still causes illness, and in extreme cases, death,” said Professor Garner. “The treatment for diarrhoea in children is pretty well known, and consists of fluids and salt. That tends to be a very effective treatment and is usually administered intravenously.”
However, Professor Garner pointed out that diarrhoea continues to cause an unacceptably large number of deaths in children in developing countries. According to the World Health Organization (WHO), in 2015, nearly nine million children under the age of five died in developing countries, with diarrhoea being second only to pneumonia as the major cause of these deaths.
Tackling the underlying infection
Today, perhaps the most frequently used non-antibiotic drug used to combat diarrhoea is Imodium, which has Loperamide as its active ingredient. It should be stressed that Loperamide does not cure diarrhoea, so much as alleviate the symptoms. What happens with diarrhoea, when the small and/or large intestine becomes irritated by whatever agent caused the diarrhoea, is that its squeezing action, which moves faecal matter and liquid through the gut, speeds up. This leaves little time for fluids and electrolytes to be absorbed by the small and large intestine, leading to runny stools and fluid and salt loss, as well as heightening the potential for abdominal cramps. Loperamide calms the gut and slows down digestion, reducing its activity and giving more time for fluids to be absorbed, resulting in firmer stools.
This can bring rapid relief to an upset stomach, but it may not cure the underlying infection and if the immune system cannot deal with the underlying infection, the condition can worsen to the point where Loperamide fails to be effective.
Dr Brown has a different approach. “The first thing to be said is that diarrhoea works on the immune system. We have two immune systems, the innate and the adaptive,” he said. The innate immune system is the body’s first line of defence. It covers all the surface areas, including internal surface areas, which means the skin, the nose, eyes, lungs and intestines – wherever the body first comes into contact with micro-organisms. “The innate immune system is very powerful, but occasionally it goes wrong, and some microorganisms can pull a jujitsu stunt on it and turn its strengths against it,” said Brown. This is what happens in part in diarrhoea. In a normal immune response, the system triggers an inflammatory reaction which acts as a call to battle for the killer cells produced by the immune system, and they clean out the troublesome bacteria.
However, with severe diarrhoea, the inflammation of the small and large intestines goes beyond what is required to trigger a reaction from the killer cells and becomes a major problem in its own right. The system keeps using more and more of the body’s fluids to try to flush out the problem and the intestines become over-active. The real danger then is that lesions develop somewhere in the gut or colon and bacteria enter the bloodstream, causing septic shock, with potentially fatal consequences.
Dr Brown’s idea is to find relatively benign ways of boosting the immune system so that it can do its job. What he wants to do, he points out, has a parallel with the latest treatments for cancer. “In cancer treatments, there is a transformation happening today. The focus is on using drugs that boost the immune system, as opposed to the traditional approach where drugs were used that killed everything, but hopefully killed the cancer cells first, since cancer cells are the most active and the fastest growing, hence react quicker to the poison.”
In 2015, nearly nine million children under the age of five died in developing countries, with diarrhoea being second only to pneumonia as the major cause of these deaths
An innovative idea
Dr Brown originally specialised in the cardiovascular field and in drug development. Three of his drug inventions are on the market today. He switched into the bacterial field about a decade ago when doing work with the Gates Foundation. “The Foundation funded a study that aimed to reduce baby and child deaths, and that made me aware of the high infant mortality figures from diarrhoea in developing countries. That inspired me to work in this field and traveller’s tummy is such a perennial and persistent problem for everyone who either has to go, or chooses to go, to foreign parts, that it was clearly the area to focus on,” he said.
The problem became a personal one for him when he started making annual trips to Tibet. “My wife and I travelled there in 2005 and we visited an orphanage there and fell in love with it. We now go there every year for two or three weeks at a time, to provide medical services to the orphanage and to the local community. The challenge, however, is that the orphanage is situated on a mountainside at 10,000 feet above sea level. It is bitterly cold for 19 hours a day and you catch infections there very easily, usually lung infections or diarrhoea, so the routine response is to prescribe antibiotics,” he recalled.
Already in South India and Tibet, the over-prescription of antibiotics has led to a very high degree of resistance to most antibiotics. “So many of our antibiotics there have a very poor chance of working, and this also held true for the antibiotics I was taking with me on the trip. I was writing up my thinking on antibiotics at the time and the problem was really scary,” he said. “WHO had produced its report on antibiotic resistance in so many microorganisms and it was clear that over prescription was a real problem.”
Dr Brown was doing his evening meditation when suddenly the idea of combining three common ingredients as a cure for diarrhoea came to him. “The idea came fully formed and from my scientific knowledge and knowledge of the immune system, I was convinced it could work,” he said.
In the time old tradition of medicine, Dr Brown’s first human subject was himself. “On my next trip to Tibet, a month later, I again had diarrhoea and painful stomach cramps. I had brought the mixture with me and within twenty minutes of my taking it, I felt fine. The stomach cramps had gone and that was the end of the diarrhoea too.”
Dr Brown was Chair of Antibiotic Research UK’s Science Committee and a trustee when he explained his diarrhoea idea to the charity and Professor Garner as CEO. The two then had a meeting in March 2017 organised by the charity with the UK Chief Medical Officer, Dame Sally Davies, who is well known for her work aimed at preventing the indiscriminate use of antibiotics around the world. Dame Sally Davies put them in touch with Professor Paul Little of Southampton University, who has contacts in Hong Kong who specialise in arranging human clinical trials.
“We are now in the process of setting up a pilot human trial. I cannot release any information about the ingredients and their combination, since one of the criteria for a blind trial is that neither the prescribing physician nor the patient knows what is being administered,” Brown explained. “This is essential since if the cure was widely covered in the press, the placebo group being used for comparative purposes could go and buy the ingredients themselves and dose themselves, rendering the study invalid.”
Dr Brown is also about to launch a website on sepsis to try to promote understanding of the fact that bacterial infections of all sorts are best treated in a more holistic way. “We need to address both the bacteria and the individual immune system, to help antibiotics be more effective in saving lives, just as we now do in cancer therapy. We are still in the Dark Ages as far as our understanding of septic shock is concerned and it can be a real killer with diarrhoea as well. So it is very much a continuation of my interest in finding a cure for traveller’s tummy,” he concluded.