Vaccinating travellers against diarrhoea using patches containing Escherichia coli toxins protects them from this unwanted ailment. And even when diarrhoea is contracted, travellers vaccinated with patches have shorter and less severe episodes. These encouraging but early results are reported in an Article published early Online and in this week's edition of The Lancet.
Enterotoxigenic* E coli (ETEC) is the leading cause of diarrhoea in travellers to endemic areas and in young children living in developing countries. Every year, some 27 million travellers and 210 million children are affected by acute diarrhoea — and the condition causes 380 000 child deaths. Travellers' diarrhoea generally lasts 4-5 days with frequent loose stools (18 per episode), usually associated with nausea, vomiting, abdominal cramps, prostration**, and dehydration. ETEC organisms are transmitted by contaminated food or drinks, and they colonise the small intestine and secrete heat-labile enterotoxin (LT) or heat-stable enterotoxin (ST). LT is found in about two-thirds of cases of ETEC diarrhoea. Previous data and studies have shown that anti-LT vaccines provide short-term protection against diarrhoea – but, whilst LT is an ideal antigen, it is too toxic to be delivered by oral, nasal, or injection routes. Thus a different mode of administration is necessary. Dr Gregory Glenn and Dr Sarah Frech, IOMAI Corporation, Gaithersburg, MD, USA, and colleagues investigated the rate of diarrhoea attacks, safety, and feasibility of a vaccine containing LT from ETEC delivered to the skin using patches in travellers.
The phase II randomised trial studied healthy adults aged 18-64 years planning to travel to Mexico or Guatemala, and who had access to a US regional vaccination centre. Patients were randomised to receive either LT (37ìg) or placebo through patches, with the two patches provided 2-3 weeks apart prior to travel. Of 201 patients recruited, 178 received patches and travelled; 170 of these were analysed. Participants tracked stool output on diary cards in country and provided samples for pathogen identification if diarrhoea occurred. Severity of diarrhoea was graded through the number of loose stools in previous 24 hours – mild (three); moderate (four or five), and severe (at least six). Patients were randomised to the placebo and LT patch groups in an approximate 2:1 ratio to increase the ability to estimate diarrhoea illness in untreated participants.
The researchers found that 24 (22%) of 111 participants receiving placebo had diarrhoea; 11 (10%) had ETEC diarrhoea. In the LT patch group, nine (15%) of 59 patients had diarrhoea; while three (5%) had ETEC diarrhoea. The rate of moderate-to-severe diarrhoea of any cause was also higher in placebo recipients (21%) than in LT-patch recipients (5%) — giving the LT patches a protective efficacy of 75% for moderate-to-severe diarrhoea. The number of cases of severe diarrhoea was also substantially higher in the placebo group (11%) than the LT patches group (2%), giving the LT patches a protective efficacy of 84%. Additionally, LT-patch recipients who became ill had shorter episodes of diarrhoea (0.5 days versus 2.1 days) with fewer loose stools (3.7 versus 10.5) than placebo.
The authors say: "The LT patch vaccine conferred some protective efficacy against moderate-to-severe travellers' diarrhoea of any cause, severe diarrhoea, and moderate-to-severe ETEC diarrhoea. Furthermore, recipients of the LT patch who became ill had a milder course of illness, with reduced stool output and duration of diarrhoea illness compared with placebo. Taken together, the LT patch conferred a meaningful benefit to the recipients."
They conclude: "In addition to the biological rationale for delivering antigen to the skin, the transcutaneous patch lends itself to a simple and needle-free application, use of the vaccine outside the cold chain***, and has been designed to be suitable for both travellers and use in the developing world. This study suggests that transcutaneous immunisation with LT in a patch could protect travellers against this common, debilitating ailment but the recorded efficacy will need confirmation in a phase III trial."
Notes to editors:
*Enterotoxic – toxic to the digestive system
**prostration - the placement of the body in a reverentially or submissively prone position. By analogy, the term is sometimes used to describe physical exhaustion or illness which results in physical collapse
***outside the cold chain – meaning no special cold/ other storage facilities are needed for the vaccine
Dr Gregory Glenn and Dr Sarah Frech, IOMAI Corporation, Gaithersburg, MD T) +1 301 556-4539 E) gglenn@iomai.com
http://www.eurekalert.org/jrnls/lance/pdfs/diarrhoeaEOP.pdf
Journal
The Lancet