Abstract: Twenty-four RCTs, including 53,247 participants, met the inclusion criteria. Four studies assessed the protective efficacy of oral cholera vaccines when used to prevent diarrhoea due to ETEC and seven studies assessed the protective efficacy of ETEC-specific vaccines. Of these 11 studies, seven studies presented efficacy data from field trials and four studies presented efficacy data from artificial challenge studies. An additional 13 trials contributed safety and immunological data only. Cholera vaccines The currently available, oral cholera killed whole cell vaccine (Dukoral®) was evaluated for protection of people against 'travellers' diarrhoea' in a single RCT in people arriving in Mexico from the USA. We did not identify any statistically significant effects on ETEC diarrhoea or all-cause diarrhoea (one trial, 502 participants, low quality evidence). Two earlier trials, one undertaken in an endemic population in Bangladesh and one undertaken in people travelling from Finland to Morocco, evaluated a precursor of this vaccine containing purified cholera toxin B subunit rather than the recombinant subunit in Dukoral®. Short term protective efficacy against ETEC diarrhoea was demonstrated, lasting for around three months (RR 0.43, 95% CI 0.26 to 0.71; two trials, 50,227 participants). This vaccine is no longer available. ETEC vaccines An ETEC-specific, killed whole cell vaccine, which also contains the recombinant cholera toxin B-subunit, was evaluated in people travelling from the USA to Mexico or Guatemala, and from Austria to Latin America, Africa, or Asia. We did not identify any statistically significant differences in ETEC-specific diarrhoea or all-cause diarrhoea (two trials, 799 participants), and the vaccine was associated with increased vomiting (RR 2.0, 95% CI 1.16 to 3.45; nine trials, 1528 participants). The other ETEC-specific vaccines in development have not yet demonstrated clinically important benefits. There is currently insufficient evidence from RCTs to support the use of the oral cholera vaccine Dukoral® for protecting travellers against ETEC diarrhoea. Further research is needed to develop safe and effective vaccines to provide both short and long-term protection against ETEC diarrhoea.

Plain-language summary: We examined the research published up to 07 December 2012. We included 24 randomized controlled trials and 53,247 participants in this review. Four studies assessed the use of oral cholera vaccines to prevent diarrhoea caused by ETEC and eight trials assessed the use of ETEC-specific vaccines to prevent diarrhoea. Seven studies presented data from field trials and four studies presented data from studies where people were artificially infected with ETEC bacteria. Also, 13 trials gave safety and immunological data only. There is currently insufficient evidence to support the use of the oral cholera vaccine Dukoral® to protect travellers against ETEC diarrhoea. Based on a single trial in people travelling from the USA to Mexico, the oral cholera vaccine Dukoral® may have little or no effect in preventing ETEC diarrhoea (one trial, 502 participants, low quality evidence). Two earlier trials, one undertaken in an endemic population in Bangladesh and one undertaken in people travelling from Finland to Morocco, evaluated a precursor of the oral cholera vaccine Dukoral®. Short term protection against ETEC diarrhoea was demonstrated, lasting for around three months (RR 0.43, 95% CI 0.26 to 0.71; two trials, 50,227 participants). However, this vaccine is no longer available. An ETEC-specific, killed whole cell vaccine, which also contains the recombinant cholera toxin B-subunit, was evaluated in people travelling from the USA to Mexico or Guatemala, and from Austria to Latin America, Africa, or Asia. There were no statistically significant differences in ETEC-specific diarrhoea or all-cause diarrhoea (two trials, 799 participants) found and the vaccine was associated with increased vomiting (RR 2.0, 95% CI 1.16 to 3.45; nine trials, 1528 participants). The other ETEC-specific vaccines in development have not yet demonstrated clinically important benefits. Further research is needed to develop safe and effective vaccines to provide both short and long-term protection against ETEC diarrhoea.