Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled fi eld trial

Methods In this phase II study, healthy adults (aged 18-64 years) who planned to travel to Mexico or Guatemala and had access to a US regional vaccination centre were eligible. A centralised randomisation code was used for allocation, which was masked to participants and site staff . Primary endpoints were to investigate the fi eld rate of ETEC diarrhoea, and to assess the safety of heat-labile toxins from E coli (LT) delivered via patch. Secondary endpoints included vaccine effi cacy against travellers' diarrhoea and ETEC. Participants were vaccinated before travel, with two patches given 2-3 weeks apart. Patches contained either 37⋅5 μg of LT or placebo. Participants tracked stool output on diary cards in country and provided samples for pathogen identifi cation if diarrhoea occurred. Diarrhoea was graded by the number of loose stools in 24 h: mild (three), moderate (four or fi ve), and severe (at least six). Analysis was per protocol. The trial is registered with ClinicalTrials.gov, number NCT00516659. Findings Recruitment closed after 201 participants were assigned patches. 178 individuals received two vaccinations and travelled and 170 were analysed. 24 (22%) of 111 placebo recipients had diarrhoea, of whom 11 (10%) had ETEC diarrhoea. The vaccine was safe and immunogenic. The 59 LT-patch recipients were protected against moderate-to-severe diarrhoea (protective effi cacy (PE) 75%, p=0⋅0070) and severe diarrhoea (PE 84%, p=0⋅0332). LT-patch recipients who became ill had shorter episodes of diarrhoea (0⋅5 days vs 2⋅1 days, p=0⋅0006) with fewer loose stools (3⋅7 vs 10⋅5, p<0⋅0001) than placebo. Interpretation Travellers' diarrhoea is a common ailment, with ETEC diarrhoea illness occurring in 10% of cases. The vaccine patch is safe and feasible, with benefi ts to the rate and severity of travellers' diarrhoea.