“'Traveller's tummy' may be cured by E. Coli patch” is the headline in The Independent today. The newspaper goes on to say that for people who get “holiday tummy, a vaccine patch can cut the incidence of traveller's diarrhoea by 75%.”
The patch is worn on the upper arm and delivers a tiny dose of toxin produced by an enterotoxigenic E. coli (ETEC) bacteria, a major cause of diarrhoea in people travelling overseas. Travellers’ diarrhoea lasts on average between four and five days, involves many trips to the toilet and can leave sufferers dehydrated. The patch is applied for a six-hour period three weeks before travel and works by stimulating the body's immune response, which then protects the traveller. A second booster patch is applied one week before travel.
This is a reliable preliminary study of volunteers from the US who travelled to Mexico and Guatemala. This study will no doubt lead to larger studies of the use of this novel vaccine and delivery system for this common and debilitating ailment.
Where did the story come from?
Sarah Frech and colleagues from the IOMAI Corporation, who produce the patch, from Gaithersburg, Maryland and other colleagues from universities and hospitals across the US carried out this research. The IOMAI Corporation provided funding for all phases of the trial. It was published in the peer-reviewed medical journal The Lancet .
What kind of scientific study was this?
This was a phase II randomised controlled trial, meaning that it was primarily a feasibility study designed to test the safety and major effects of the patch in a relatively small number of patients. Larger phase III studies would usually be required to show conclusively that a product was effective.
The researchers recruited 201 healthy adults (aged 18–64 years) who planned to travel to Mexico or Guatemala from the US and who could reach one of 14 US regional vaccination centres. They did not accept volunteers who had had travellers' diarrhoea before or who had travelled to an endemic country in the previous year, had previously used this or some other vaccines, or had had significant illness, were immunosuppressed or were pregnant, nursing or unwilling to use an effective form of birth control.
The participants were examined at the start of the trial, and randomisation took place centrally. Along with the investigators, the participants were blind to their allocation, in that they were all unaware of whether they had received the active patch or a placebo. The vaccine patch contained a toxin derived from the bacterium enterotoxigenic E. coli (ETEC). The vaccine or placebo patch was given to patients while they visited the centre, and was left on the arm for six hours. Patches were placed on alternate upper arms a minimum of three weeks (first vaccination) and one week (second vaccination) before departure.
After they arrived at their destination, the volunteers reported to a clinic every week. They kept a diary in which they recorded any diarrhoea, the number of times they went to the toilet, and other symptoms. Mild diarrhoea was defined as three loose stools in 24 hours, moderate diarrhoea was four to five loose stools and severe diarrhoea was at least six loose stools in 24 hours. The local investigators tested specimens and recorded the number of cases of ETEC diarrhoea and other diarrhoeas among the cases of diarrhoea.
What were the results of the study?
At the end of the trial data was available for 170 people. In the placebo group 24 out of 111 (22%) had diarrhoea, of whom 11 (10%) had ETEC diarrhoea. In the vaccine group, nine out of 59 (15%) had diarrhoea, and three (5%) had ETEC diarrhoea. The vaccine was safe and immunogenic.
The vaccine patch protected against moderate-to-severe diarrhoea and severe diarrhoea of any cause, and this result was statistically significant. For ETEC diarrhoea, the reduction in diarrhoea was not significant. If they became ill with ETEC or any diarrhoea, the vaccine group had shorter episodes (about 1.5 days less) of diarrhoea with about five to seven fewer loose stools than the people who had received the placebo patch.
What interpretations did the researchers draw from these results?
The researchers interpret their results by saying “travellers' diarrhoea is a common ailment, with ETEC diarrhoea illness occurring in 10% of cases. The vaccine patch is safe and feasible, with benefits to the rate and severity of travellers’ diarrhoea.”
What does the NHS Knowledge Service make of this study?
This reliable phase II study has reported preliminary results for this new vaccine. There are some points that the researchers make regarding their interpretations:
- This study aimed to recruit enough people to demonstrate the logistics of a future large trial in Mexico and Guatemala. By estimating the number of people who develop travellers' diarrhoea in the placebo group, the researchers would be able to estimate how many people would be needed for the larger trial to show an effect. They did not aim to recruit sufficient people in this study (to “power” the trial) for efficacy. For this reason, some of the results did not show statistical significance, but a trend towards efficacy was demonstrated.
- The researchers looked at two sources of bias or factors that could potentially mislead them in their conclusions. The duration of surveillance could be different between the groups who had received the vaccine patch compared with the placebo. In fact, the groups did not differ on this measure. It was also thought possible that those in the placebo group might use antibiotics to treat their diarrhoea more often than those who had received active patches. The researchers looked for this and found that the antibiotic ciprofloxacin was used in three (33%) of nine participants in the patch group, compared with 16 (66%) of 24 participants in the placebo group. This increased antibiotic use in the placebo group could have reduced the severity and duration of diarrhoea, and swung the results in favour of the placebo group.
The researchers comment that a large number of placebo recipients with diarrhoea were quite ill, even after taking antibiotics, and as a group they had an average of more than ten stools per episode. This suggests that travellers' diarrhoea is far more than an inconvenience to travellers even when antibiotic treatment is used. This provides further justification for developing preventive treatments such as this vaccine.
Sir Muir Gray adds...
Looks promising, but remember, prevention is better than cure.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Independent, 12 June 2008
The Daily Telegraph, 12 June 2008
Daily Mail, 12 June 2008
BBC News, 12 June 2008
Links to the science
Lancet 2008; Jun 12 [Epub ahead of print]